Hassan Abolhassani | Karolinska University Hospital (original) (raw)

Papers by Hassan Abolhassani

Research paper thumbnail of Autoimmune versus Non-autoimmune Cutaneous Features in Monogenic Patients with Inborn Errors of Immunity

Biology

Cutaneous manifestations are one of the most common presentations among patients with inborn erro... more Cutaneous manifestations are one of the most common presentations among patients with inborn errors of immunity (IEI). These skin manifestations are often among the first presenting features in the majority of patients preceding the IEI diagnosis. We studied 521 available monogenic patients with IEI listed in the Iranian IEI registry up to November 2022. We extracted each patient’s demographic information, detailed clinical history of cutaneous manifestations, and immunologic evaluations. The patients were then categorized and compared based on their phenotypical classifications provided by the International Union of Immunological Societies. Most patients were categorized into syndromic combined immunodeficiency (25.1%), non-syndromic combined immunodeficiency (24.4%), predominantly antibody deficiency (20.7%), and diseases of immune dysregulation (20.5%). In total, 227 patients developed skin manifestations at a median (IQR) age of 2.0 (0.5–5.2) years; a total of 66 (40.7%) of thes...

Research paper thumbnail of Updates on Molecular Pathogenesis of Non-Hodgkin’s Lymphoma

Interdisciplinary Cancer Research

Research paper thumbnail of Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features

Frontiers in Immunology

BackgroundCombined immune deficiencies (CIDs) with associated or syndromic features are a highly ... more BackgroundCombined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions.MethodsWe analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations.ResultsA total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, we...

Research paper thumbnail of Updates of cancer hallmarks in patients with inborn errors of immunity

Current Opinion in Allergy & Clinical Immunology

Research paper thumbnail of Comprehensive Assessment of Skin Disorders in Patients with Common Variable Immunodeficiency (CVID)

Journal of Clinical Immunology

BACKGROUND Common variable immunodeficiency (CVID) is an inborn error of immunity (IEI) character... more BACKGROUND Common variable immunodeficiency (CVID) is an inborn error of immunity (IEI) characterized by various clinical manifestations such as hypogammaglobulinemia, recurrent infections, and autoimmune diseases. Among different clinical manifestations, skin manifestations have been less reported in these patients. METHODS In this study, we investigated the prevalence of dermatologic features in 387 CVID patients. Demographic information, clinical manifestations, laboratory data, and genetic findings were collected from medical records. All data were analyzed based on the presence or absence of skin disorders in CVID patients. RESULTS We observed at least one skin manifestation in about 40% of these patients. Among these complications, skin infection (n = 64, 42.1%) was the most frequent presentation, followed by non-infectious skin lesions (n = 54, 35.6%). Among skin infections, abscesses (n = 34, 22.4%) were the most common complication. Skin infections such as cellulitis, impetigo, measles, and warts were also documented. Eczema (n = 34, 22.4%) was the most common complication in atopic lesions, and vitiligo (n = 13, 8.5%) was prevalent in autoimmune/pigmentation disorders. Among all the patients with genetic mutations, one-quarter had a deleterious mutation in the LRBA gene, relating to the autoimmune and atopic skin lesions. CONCLUSION This rate of skin disorders in our cohort demonstrating these manifestations could be significant in CVID patients, and they are not rare. Low data of skin complications in CVID patients could be attributed to insufficient attention of physicians and also might alert dermatologists to perform immunological investigations in children with certain skin manifestations.

Research paper thumbnail of Evidence-Based Immunotherapeutic Effects of Herbal Compounds on Humoral Immunity: Ancient and New Approaches

Chinese Journal of Integrative Medicine

The human immune system represents a dynamic multiscale system with high complexity in biology. H... more The human immune system represents a dynamic multiscale system with high complexity in biology. Humoral immunity, as the main branch of adaptive immunity, is characterized by differentiated stages of the B lymphocytes, producing the final product of antibodies that has a diversity of the tuning mechanisms within genetic and epigenetic levels in confrontation with environmental exposures. Disorders because of disturbed humoral immunity are linked with dysregulation of feedback-regulated signaling and the dynamic of immune components that determine the overall response. Food products, mainly herbal components have a significant role in tailoring the immune system micro-ecosystem which can diversify the adaptive nature of humoral immunity. Herein, we review the current evidence-based approaches for the impact of medicinal herbs on humoral immunity signaling and antibody production with a focus on immunotherapeutic applications.

Research paper thumbnail of Atypical Ataxia Presentation in Variant Ataxia Telangiectasia: Iranian Case-Series and Review of the Literature

Frontiers in Immunology, 2022

Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. ... more Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype wi...

Research paper thumbnail of Specific Immune Response and Cytokine Production in CD70 Deficiency

Frontiers in Pediatrics, 2021

Collective clinical and immunologic findings of defects in the CD27–CD70 axis indicate a primary ... more Collective clinical and immunologic findings of defects in the CD27–CD70 axis indicate a primary immunodeficiency associated with terminal B-cell development defect and immune dysregulation leading to autoimmunity, uncontrolled viral infection, and lymphoma. Since the molecular mechanism underlying this entity of primary immunodeficiency has been recently described, more insight regarding the function and profile of immunity is required. Therefore, this study aimed to investigate stimulated antibody production, polyclonal vs. virus-specific T-cell response, and cytokine production of a CD70-deficient patient reported previously with early-onset antibody deficiency suffering from chronic viral infections and B-cell lymphoma. The patient and her family members were subjected to clinical evaluation, immunological assays, and functional analyses. The findings of this study indicate an impaired ability of B cells to produce immunoglobulins, and a poor effector function of T cells was als...

Research paper thumbnail of Semi-automatic Context-aware Composition of Context-aware Semantic Web Services

In many cases, atomic Web services are not able to provide requested functionality. Therefore, th... more In many cases, atomic Web services are not able to provide requested functionality. Therefore, the composition task is required on available atomic services. In addition, Context awareness in Web services is gaining momentum as the opportunity to benefit the interactions between human, applications and the environment. So, it seems reasonable to use available context information in composition procedure to provide a composite Semantic Web service which is adapted to the context of participant Web services and user. In this paper, we introduce a novel approach for semi-automatic context-aware composition of stateless context-aware Semantic Web Services. One of the main characteristics of proposed approach is the ability of considering the degree of context-awareness of the service in the composition procedure. Moreover, we use a new schema for Semantic Web service description which is able to represent both functional and non-functional information about context-aware Semantic Web services.

Research paper thumbnail of Hallmarks of Cancers: Primary Antibody Deficiency Versus Other Inborn Errors of Immunity

Frontiers in Immunology, 2021

Inborn Errors of Immunity (IEI) comprise more than 450 inherited diseases, from which selected pa... more Inborn Errors of Immunity (IEI) comprise more than 450 inherited diseases, from which selected patients manifest a frequent and early incidence of malignancies, mainly lymphoma and leukemia. Primary antibody deficiency (PAD) is the most common form of IEI with the highest proportion of malignant cases. In this review, we aimed to compare the oncologic hallmarks and the molecular defects underlying PAD with other IEI entities to dissect the impact of avoiding immune destruction, genome instability, and mutation, enabling replicative immortality, tumor-promoting inflammation, resisting cell death, sustaining proliferative signaling, evading growth suppressors, deregulating cellular energetics, inducing angiogenesis, and activating invasion and metastasis in these groups of patients. Moreover, some of the most promising approaches that could be clinically tested in both PAD and IEI patients were discussed.

Research paper thumbnail of Genetic Risk Variants for Class Switching Recombination Defects in Ataxia-Telangiectasia Patients

Journal of Clinical Immunology, 2021

Background Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations... more Background Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. A-T patients manifest considerable variability in clinical and immunological features, suggesting the presence of genetic modifying factors. A striking heterogeneity has been observed in class switching recombination (CSR) in A-T patients which cannot be explained by the severity of ATM mutations. Methods To investigate the cause of variable CSR in A-T patients, we applied whole-exome sequencing (WES) in 20 A-T patients consisting of 10 cases with CSR defect (CSR-D) and 10 controls with normal CSR (CSR-N). Comparative analyses on modifier variants found in the exomes of these two groups of patients were performed. Results For the first time, we identified some variants in the exomes of the CSR-D group that were significantly associated with antigen processing and presentation pathway. Moreover, in this group of patients, the variants in f...

Research paper thumbnail of Known and potential molecules associated with altered B cell development leading to predominantly antibody deficiencies

Pediatric Allergy and Immunology, 2021

Predominantly antibody deficiencies (PADs) encompass a heterogeneous group of disorders character... more Predominantly antibody deficiencies (PADs) encompass a heterogeneous group of disorders characterized by low immunoglobulin serum levels in the presence or absence of peripheral B cells. Clinical presentation of affected patients may include recurrent respiratory and gastrointestinal infections, invasive infections, autoimmune manifestations, allergic reactions, lymphoproliferation, and increased susceptibility to malignant transformation. In the last decades, several genetic alterations affecting B‐cell development/maturation have been identified as causative of several forms of PADs, adding important information on the genetic background of PADs, which in turn should lead to a better understanding of these disorders and precise clinical management of affected patients. This review aimed to present a comprehensive overview of the known and potentially involved molecules in the etiology of PADs to elucidate the pathogenesis of these disorders and eventually offer a better prognosis for affected patients.

Research paper thumbnail of Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency

Genetics in medicine : official journal of the American College of Medical Genetics, Jan 19, 2018

The etiology of 80% of patients with primary antibody deficiency (PAD), the second most common ty... more The etiology of 80% of patients with primary antibody deficiency (PAD), the second most common type of human immune system disorder after human immunodeficiency virus infection, is yet unknown. Clinical/immunological phenotyping and exome sequencing of a cohort of 126 PAD patients (55.5% male, 95.2% childhood onset) born to predominantly consanguineous parents (82.5%) with unknown genetic defects were performed. The American College of Medical Genetics and Genomics criteria were used for validation of pathogenicity of the variants. This genetic approach and subsequent immunological investigations identified potential disease-causing variants in 86 patients (68.2%); however, 27 of these patients (31.4%) carried autosomal dominant (24.4%) and X-linked (7%) gene defects. This genetic approach led to the identification of new phenotypes in 19 known genes (38 patients) and the discovery of a new genetic defect (CD70 pathogenic variants in 2 patients). Medical implications of a definite g...

Research paper thumbnail of Our thanks to those who have helped with this issue of Expert Review of Clinical Immunology. Listed below are the authors, referees and others who have kindly given their time, effort and expertise; their generosity has helped establish this publication

Research paper thumbnail of In Vitro Chromosomal Radiosensitivity in Patients and in Carriers with Abnormal non-Down's Syndrome Karyotypes

Pediatric Research, 1972

Chromosomal aberrations lymphocytes fibroblasts radiosensitivity, karyotype chromosomal

Research paper thumbnail of Clinical, Immunological and Genetic Spectrum Of Novel BTK Gene Mutations In X-Linked Agammaglobulinemia Patients and Female Carriers

Journal of Allergy and Clinical Immunology, 2014

In X-linked agammaglobulinemia (XLA) though over 600 mutations have been reported in the BTK gene... more In X-linked agammaglobulinemia (XLA) though over 600 mutations have been reported in the BTK gene, new mutations continue to be identified and characterized. We report 18 novel mutations not previously described in 30 male patients with a clinical phenotype of XLA as well as female carriers with male relatives. METHODS: Btk protein was assessed by flow cytometry and mutation analysis with full-gene Sanger sequencing. RESULTS: Of the 18 novel mutations, 9 were missense, 2 nonsense, 3 deletions leading to frameshift, 1 deletion and 1 frameshift duplication. Seven of the new mutations were identified in more than one individual, from the same family or unrelated, male or female. Of all the mutations, 17% (n53) were identified in patients diagnosed for the first time in adulthood (age range: 30-64y). Twenty of 23 male (9 normal, 11 reduced or absent protein) patients and 4 of the 7 female carriers had Btk protein analysis performed by flow cytometry. All female carriers had normal Btk protein expression. Of the 23 male patients, 20 had undetectable or <2% B cells (B cell data not available for 3 patients). All but one of the male patients had hypogammaglobulinemia. All mutations were predicted to be deleterious. CONCLUSIONS: The spectrum of protein expression, B cell numbers and new gene defects enforces the necessity of detailed diagnostic work-up in patients suspected of having XLA, especially as several patients may be diagnosed for the first time in mid-to-late adulthood.

Research paper thumbnail of Our thanks to those who have helped with this issue of Expert Review of Neurotherapeutics. Listed below are the authors, referees and others who have kindly given their time, effort and expertise; their generosity has helped establish this publication

Research paper thumbnail of Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Journal of Clinical Immunology, 2021

Background Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immun... more Background Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity wa...

Research paper thumbnail of Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity

Pediatric Allergy and Immunology

Research paper thumbnail of Global systematic review of primary immunodeficiency registries

Expert Review of Clinical Immunology

Introduction: During the last 4 decades, registration of patients with primary immunodeficiencies... more Introduction: During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered: Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion: Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.

Research paper thumbnail of Autoimmune versus Non-autoimmune Cutaneous Features in Monogenic Patients with Inborn Errors of Immunity

Biology

Cutaneous manifestations are one of the most common presentations among patients with inborn erro... more Cutaneous manifestations are one of the most common presentations among patients with inborn errors of immunity (IEI). These skin manifestations are often among the first presenting features in the majority of patients preceding the IEI diagnosis. We studied 521 available monogenic patients with IEI listed in the Iranian IEI registry up to November 2022. We extracted each patient’s demographic information, detailed clinical history of cutaneous manifestations, and immunologic evaluations. The patients were then categorized and compared based on their phenotypical classifications provided by the International Union of Immunological Societies. Most patients were categorized into syndromic combined immunodeficiency (25.1%), non-syndromic combined immunodeficiency (24.4%), predominantly antibody deficiency (20.7%), and diseases of immune dysregulation (20.5%). In total, 227 patients developed skin manifestations at a median (IQR) age of 2.0 (0.5–5.2) years; a total of 66 (40.7%) of thes...

Research paper thumbnail of Updates on Molecular Pathogenesis of Non-Hodgkin’s Lymphoma

Interdisciplinary Cancer Research

Research paper thumbnail of Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features

Frontiers in Immunology

BackgroundCombined immune deficiencies (CIDs) with associated or syndromic features are a highly ... more BackgroundCombined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions.MethodsWe analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations.ResultsA total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, we...

Research paper thumbnail of Updates of cancer hallmarks in patients with inborn errors of immunity

Current Opinion in Allergy & Clinical Immunology

Research paper thumbnail of Comprehensive Assessment of Skin Disorders in Patients with Common Variable Immunodeficiency (CVID)

Journal of Clinical Immunology

BACKGROUND Common variable immunodeficiency (CVID) is an inborn error of immunity (IEI) character... more BACKGROUND Common variable immunodeficiency (CVID) is an inborn error of immunity (IEI) characterized by various clinical manifestations such as hypogammaglobulinemia, recurrent infections, and autoimmune diseases. Among different clinical manifestations, skin manifestations have been less reported in these patients. METHODS In this study, we investigated the prevalence of dermatologic features in 387 CVID patients. Demographic information, clinical manifestations, laboratory data, and genetic findings were collected from medical records. All data were analyzed based on the presence or absence of skin disorders in CVID patients. RESULTS We observed at least one skin manifestation in about 40% of these patients. Among these complications, skin infection (n = 64, 42.1%) was the most frequent presentation, followed by non-infectious skin lesions (n = 54, 35.6%). Among skin infections, abscesses (n = 34, 22.4%) were the most common complication. Skin infections such as cellulitis, impetigo, measles, and warts were also documented. Eczema (n = 34, 22.4%) was the most common complication in atopic lesions, and vitiligo (n = 13, 8.5%) was prevalent in autoimmune/pigmentation disorders. Among all the patients with genetic mutations, one-quarter had a deleterious mutation in the LRBA gene, relating to the autoimmune and atopic skin lesions. CONCLUSION This rate of skin disorders in our cohort demonstrating these manifestations could be significant in CVID patients, and they are not rare. Low data of skin complications in CVID patients could be attributed to insufficient attention of physicians and also might alert dermatologists to perform immunological investigations in children with certain skin manifestations.

Research paper thumbnail of Evidence-Based Immunotherapeutic Effects of Herbal Compounds on Humoral Immunity: Ancient and New Approaches

Chinese Journal of Integrative Medicine

The human immune system represents a dynamic multiscale system with high complexity in biology. H... more The human immune system represents a dynamic multiscale system with high complexity in biology. Humoral immunity, as the main branch of adaptive immunity, is characterized by differentiated stages of the B lymphocytes, producing the final product of antibodies that has a diversity of the tuning mechanisms within genetic and epigenetic levels in confrontation with environmental exposures. Disorders because of disturbed humoral immunity are linked with dysregulation of feedback-regulated signaling and the dynamic of immune components that determine the overall response. Food products, mainly herbal components have a significant role in tailoring the immune system micro-ecosystem which can diversify the adaptive nature of humoral immunity. Herein, we review the current evidence-based approaches for the impact of medicinal herbs on humoral immunity signaling and antibody production with a focus on immunotherapeutic applications.

Research paper thumbnail of Atypical Ataxia Presentation in Variant Ataxia Telangiectasia: Iranian Case-Series and Review of the Literature

Frontiers in Immunology, 2022

Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. ... more Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype wi...

Research paper thumbnail of Specific Immune Response and Cytokine Production in CD70 Deficiency

Frontiers in Pediatrics, 2021

Collective clinical and immunologic findings of defects in the CD27–CD70 axis indicate a primary ... more Collective clinical and immunologic findings of defects in the CD27–CD70 axis indicate a primary immunodeficiency associated with terminal B-cell development defect and immune dysregulation leading to autoimmunity, uncontrolled viral infection, and lymphoma. Since the molecular mechanism underlying this entity of primary immunodeficiency has been recently described, more insight regarding the function and profile of immunity is required. Therefore, this study aimed to investigate stimulated antibody production, polyclonal vs. virus-specific T-cell response, and cytokine production of a CD70-deficient patient reported previously with early-onset antibody deficiency suffering from chronic viral infections and B-cell lymphoma. The patient and her family members were subjected to clinical evaluation, immunological assays, and functional analyses. The findings of this study indicate an impaired ability of B cells to produce immunoglobulins, and a poor effector function of T cells was als...

Research paper thumbnail of Semi-automatic Context-aware Composition of Context-aware Semantic Web Services

In many cases, atomic Web services are not able to provide requested functionality. Therefore, th... more In many cases, atomic Web services are not able to provide requested functionality. Therefore, the composition task is required on available atomic services. In addition, Context awareness in Web services is gaining momentum as the opportunity to benefit the interactions between human, applications and the environment. So, it seems reasonable to use available context information in composition procedure to provide a composite Semantic Web service which is adapted to the context of participant Web services and user. In this paper, we introduce a novel approach for semi-automatic context-aware composition of stateless context-aware Semantic Web Services. One of the main characteristics of proposed approach is the ability of considering the degree of context-awareness of the service in the composition procedure. Moreover, we use a new schema for Semantic Web service description which is able to represent both functional and non-functional information about context-aware Semantic Web services.

Research paper thumbnail of Hallmarks of Cancers: Primary Antibody Deficiency Versus Other Inborn Errors of Immunity

Frontiers in Immunology, 2021

Inborn Errors of Immunity (IEI) comprise more than 450 inherited diseases, from which selected pa... more Inborn Errors of Immunity (IEI) comprise more than 450 inherited diseases, from which selected patients manifest a frequent and early incidence of malignancies, mainly lymphoma and leukemia. Primary antibody deficiency (PAD) is the most common form of IEI with the highest proportion of malignant cases. In this review, we aimed to compare the oncologic hallmarks and the molecular defects underlying PAD with other IEI entities to dissect the impact of avoiding immune destruction, genome instability, and mutation, enabling replicative immortality, tumor-promoting inflammation, resisting cell death, sustaining proliferative signaling, evading growth suppressors, deregulating cellular energetics, inducing angiogenesis, and activating invasion and metastasis in these groups of patients. Moreover, some of the most promising approaches that could be clinically tested in both PAD and IEI patients were discussed.

Research paper thumbnail of Genetic Risk Variants for Class Switching Recombination Defects in Ataxia-Telangiectasia Patients

Journal of Clinical Immunology, 2021

Background Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations... more Background Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. A-T patients manifest considerable variability in clinical and immunological features, suggesting the presence of genetic modifying factors. A striking heterogeneity has been observed in class switching recombination (CSR) in A-T patients which cannot be explained by the severity of ATM mutations. Methods To investigate the cause of variable CSR in A-T patients, we applied whole-exome sequencing (WES) in 20 A-T patients consisting of 10 cases with CSR defect (CSR-D) and 10 controls with normal CSR (CSR-N). Comparative analyses on modifier variants found in the exomes of these two groups of patients were performed. Results For the first time, we identified some variants in the exomes of the CSR-D group that were significantly associated with antigen processing and presentation pathway. Moreover, in this group of patients, the variants in f...

Research paper thumbnail of Known and potential molecules associated with altered B cell development leading to predominantly antibody deficiencies

Pediatric Allergy and Immunology, 2021

Predominantly antibody deficiencies (PADs) encompass a heterogeneous group of disorders character... more Predominantly antibody deficiencies (PADs) encompass a heterogeneous group of disorders characterized by low immunoglobulin serum levels in the presence or absence of peripheral B cells. Clinical presentation of affected patients may include recurrent respiratory and gastrointestinal infections, invasive infections, autoimmune manifestations, allergic reactions, lymphoproliferation, and increased susceptibility to malignant transformation. In the last decades, several genetic alterations affecting B‐cell development/maturation have been identified as causative of several forms of PADs, adding important information on the genetic background of PADs, which in turn should lead to a better understanding of these disorders and precise clinical management of affected patients. This review aimed to present a comprehensive overview of the known and potentially involved molecules in the etiology of PADs to elucidate the pathogenesis of these disorders and eventually offer a better prognosis for affected patients.

Research paper thumbnail of Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency

Genetics in medicine : official journal of the American College of Medical Genetics, Jan 19, 2018

The etiology of 80% of patients with primary antibody deficiency (PAD), the second most common ty... more The etiology of 80% of patients with primary antibody deficiency (PAD), the second most common type of human immune system disorder after human immunodeficiency virus infection, is yet unknown. Clinical/immunological phenotyping and exome sequencing of a cohort of 126 PAD patients (55.5% male, 95.2% childhood onset) born to predominantly consanguineous parents (82.5%) with unknown genetic defects were performed. The American College of Medical Genetics and Genomics criteria were used for validation of pathogenicity of the variants. This genetic approach and subsequent immunological investigations identified potential disease-causing variants in 86 patients (68.2%); however, 27 of these patients (31.4%) carried autosomal dominant (24.4%) and X-linked (7%) gene defects. This genetic approach led to the identification of new phenotypes in 19 known genes (38 patients) and the discovery of a new genetic defect (CD70 pathogenic variants in 2 patients). Medical implications of a definite g...

Research paper thumbnail of Our thanks to those who have helped with this issue of Expert Review of Clinical Immunology. Listed below are the authors, referees and others who have kindly given their time, effort and expertise; their generosity has helped establish this publication

Research paper thumbnail of In Vitro Chromosomal Radiosensitivity in Patients and in Carriers with Abnormal non-Down's Syndrome Karyotypes

Pediatric Research, 1972

Chromosomal aberrations lymphocytes fibroblasts radiosensitivity, karyotype chromosomal

Research paper thumbnail of Clinical, Immunological and Genetic Spectrum Of Novel BTK Gene Mutations In X-Linked Agammaglobulinemia Patients and Female Carriers

Journal of Allergy and Clinical Immunology, 2014

In X-linked agammaglobulinemia (XLA) though over 600 mutations have been reported in the BTK gene... more In X-linked agammaglobulinemia (XLA) though over 600 mutations have been reported in the BTK gene, new mutations continue to be identified and characterized. We report 18 novel mutations not previously described in 30 male patients with a clinical phenotype of XLA as well as female carriers with male relatives. METHODS: Btk protein was assessed by flow cytometry and mutation analysis with full-gene Sanger sequencing. RESULTS: Of the 18 novel mutations, 9 were missense, 2 nonsense, 3 deletions leading to frameshift, 1 deletion and 1 frameshift duplication. Seven of the new mutations were identified in more than one individual, from the same family or unrelated, male or female. Of all the mutations, 17% (n53) were identified in patients diagnosed for the first time in adulthood (age range: 30-64y). Twenty of 23 male (9 normal, 11 reduced or absent protein) patients and 4 of the 7 female carriers had Btk protein analysis performed by flow cytometry. All female carriers had normal Btk protein expression. Of the 23 male patients, 20 had undetectable or <2% B cells (B cell data not available for 3 patients). All but one of the male patients had hypogammaglobulinemia. All mutations were predicted to be deleterious. CONCLUSIONS: The spectrum of protein expression, B cell numbers and new gene defects enforces the necessity of detailed diagnostic work-up in patients suspected of having XLA, especially as several patients may be diagnosed for the first time in mid-to-late adulthood.

Research paper thumbnail of Our thanks to those who have helped with this issue of Expert Review of Neurotherapeutics. Listed below are the authors, referees and others who have kindly given their time, effort and expertise; their generosity has helped establish this publication

Research paper thumbnail of Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Journal of Clinical Immunology, 2021

Background Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immun... more Background Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity wa...

Research paper thumbnail of Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity

Pediatric Allergy and Immunology

Research paper thumbnail of Global systematic review of primary immunodeficiency registries

Expert Review of Clinical Immunology

Introduction: During the last 4 decades, registration of patients with primary immunodeficiencies... more Introduction: During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered: Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion: Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.