Roberto Perniola - Academia.edu (original) (raw)

Papers by Roberto Perniola

Frontiers of Hormone Research, 2016

Autoimmune Addison's disease (AAD) is a complex disease that results from the interaction of ... more Autoimmune Addison's disease (AAD) is a complex disease that results from the interaction of a predisposing genetic background with still unknown environmental factors. Pathogenic variants in the autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrine syndrome type 1, of which AAD is a major disease component. Among the genetic factors for isolated AAD and autoimmune polyendocrine syndrome type 2, a key role is played by HLA class II genes: HLA-DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*04-DQA1*0301-DQB1*0302 are positively, and DRB1*0403 is negatively, associated with genetic risk for AAD. The MHC class I chain-related gene A (MICA) allele 5.1 is strongly and positively associated with AAD. Other gene polymorphisms contribute to the genetic risk for AAD, including CIITA (MHC class II transactivator), the master regulator of MHC class II expression, cytotoxic T-lymphocyte antigen-4 (CTLA-4), PTPN22, STAT4, PD-L1, NALP1, FCRL3, GPR174, GATA3, NFATC1, CYP27B1 and the vitamin D receptor.

PubMed, Dec 1, 1999

Background: Many advances have been made in the sensitivity of assays for hepatitis C virus antib... more Background: Many advances have been made in the sensitivity of assays for hepatitis C virus antibodies (HCV-Ab). Nevertheless, polymerase chain reaction (PCR) is still the best method to establish if infection has become chronic. In this study we utilised third-generation assays for HCV-Ab in a four-year follow-up to determine the trend in antibody levels in currently and past infected patients. Methods: Seventy-two multitransfused subjects were enrolled. All the patients were reactive at the first test with third-generation screening and confirmatory assays (ELISA-3 and RIBA-3) for HCV-Ab. They were subsequently retested in a follow-up ranging from 41 to 47 months. Viraemia was investigated with a standardised PCR kit; negative samples were reevaluated with nested PCR. Differences in antibody trend were calculated with the Wilcoxon signed-rank test. Results: No statistical variation in antibody titre was found in the 41 HCV-RNA positive patients, although some of these showed a decrease in anti-c100p level. In contrast, anti-c22p, anti-c33c and anti-c100p levels decreased significantly in the 19 past infected patients. Twelve patients were HCV-RNA negative or intermittently positive with commercial PCR test, and consistently or intermittently positive in nested PCR: in these patients, antibody trend varied. Conclusions: Although resolving hepatitis is associated with a decrease in antibody titre, the trend should be observed for a long period to distinguish between chronic and past infection. However, the evaluation in a single patient can be unreliable. Since a doubtful response for HCV-RNA is in some cases obtained, further improvements in the diagnosis of chronic HCV infection are needed.

The Journal of Clinical Endocrinology and Metabolism, May 1, 2015

Context: NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER... more Context: NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER) is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1) but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis. Objectives: The objectives of the study were to determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison's disease (AAD) and to evaluate whether inhibin chains are a target for autoantibodies in POI. Methods: Autoantibodies against NALP5/MATER and inhibin chains-␣ and-␤A were determined by radiobinding assays in 172 patients with AAD without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI [steroidogenic cell autoimmune POI (SCA-POI)], 119 women with idiopathic POI, 19 patients with APS1, and 211 healthy control subjects. Results: NALP5/MATER-Ab were detected in 11 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P Ͻ .001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin chain-␣/␤A autoantibodies. Conclusions: NALP5/MATER-Ab are associated with hypoparathyroidism in APS1 but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.

Journal of Pediatric Endocrinology and Metabolism, 2005

PURPOSE: To determine changes that take place in the sub populations of peripheral blood mononucl... more PURPOSE: To determine changes that take place in the sub populations of peripheral blood mononuclear cells of patients with MDR-tuberculosis and to compare their immune profile to responders to anti-tuberculosis drugs and healthy controls.

Journal of Endocrinological Investigation, 2007

Mycoses, May 1, 2008

... How to Cite. Perniola, R., Congedo, M., Rizzo, A., Damiani, AS, Faneschi, ML, Pizzolante, M. ... more ... How to Cite. Perniola, R., Congedo, M., Rizzo, A., Damiani, AS, Faneschi, ML, Pizzolante, M. and Lobreglio, G. (2008), Innate and adaptive immunity in patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy. Mycoses, 51: 228–235. ...

European journal of endocrinology, Oct 1, 2000

Objective: The aim of the study was to assess the complex of autoantibodies which can be detected... more Objective: The aim of the study was to assess the complex of autoantibodies which can be detected in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare autosomal recessive disease in which the extent of autoimmunity is still unknown. Design: Antibodies (A) to parathyroid glands, adrenal cortex (AC-A), ovary and testis (steroid cell antibodies, SC-A), pancreatic islet cells (IC-A), gastric parietal cells, and non-organ-speci®c antigens were investigated in 11 APECED patients living in the Salento region of southern Italy. Further measurements included antibodies to cytochrome P450 (CYP) enzymes: cholesterol side-chain cleavage enzyme (CYP11A), 21-hydroxylase (CYP21) and 17a-hydroxylase (CYP17); and to glutamic acid decarboxylase 65-kDa isoform (GAD65), tyrosine phosphatase-like protein IA2, thyroglobulin (TG), thyroperoxidase (TPO), thyrotropin receptor, liver CYP enzymes and intrinsic factor. Methods: Antibodies to organs and subcellular fractions were detected by immuno¯uorescence. Radiobinding, immunoradiometric, and immunoblotting assays were used for the other measurements. Results: AC-A and SC-A were positive in all sera; among antibodies to adrenal CYP enzymes, only CYP21-A were present in all the patients with Addison's disease of short-medium duration (<15 years). Of three patients with Addison's disease of long duration (>15 years), two tested positive for antibodies to all three CYP enzymes, and the other for only CYP11A-A. In all sera CYP11A-A and/or CYP17-A were found. Two patients tested positive for both IC-A and GAD65-A, one for both IC-A and IA2-A, and one for GAD65-A; the fasting C-peptide assay showed no statistical difference between these four subjects and the others. All four hypothyroid patients were positive for TPO-A, while two of them were positive and two were negative for TG-A; two euthyroid subjects had positivity for TG-A. Liver-kidney microsomal antibodies reacting against the CYP2A6 were detected in two patients with autoimmune hepatitis. All but one sera contained anti-nuclear antibodies at a titre ranging between 1:20 and 1:80; however, only two patients had a connective tissue disease (Sjo Ègren's syndrome). Conclusions: Several autoantibodies may be detected in any APECED patient. Our data con®rm that CYP21-A and TPO-A are major autoantibodies involved in APECED-associated Addison's disease and hypothyroidism respectively, while CYP11A-A and CYP17-A correlate with positivity for SC-A. Markers of islet cell autoimmunity are frequent, but prevalence and modalities of progression to overt b-cell failure have to be clari®ed. Low-titre non-organ-speci®c autoantibodies are a feature of autoimmunity in APECED, but their role has yet to be fully explained.

Frontiers in Immunology, Feb 26, 2021

The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoi... more The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator (AIRE) gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)-chronic mucocutaneous candidiasis-autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.

European journal of endocrinology, Aug 1, 2010

Objective: Steroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantib... more Objective: Steroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantibodies (21OHAbs), 17a-hydroxylase autoantibodies (17OHAb), and cholesterol side-chain cleavage enzyme (side-chain cleavage autoantibodies, P450sccAb) characterize autoimmune primary ovarian insufficiency (SCA-POI). The aim of the study was to analyze IgG subclass specificity of autoantibodies related to adrenal and ovarian autoimmunity. Design: We studied 29 women with SCA-POI, 30 women with autoimmune Addison's disease (AAD) without POI, and 14 patients with autoimmune polyendocrine syndrome type 1 (APS1). 21OHAb isotypes were also analyzed in 14 subjects with preclinical AAD. Samples from 30 healthy women served as control group to determine the upper level of normality in the isotype assays. Methods: Immunoradiometric assays with IgG subclass-specific secondary antibodies. Results: In 21OHAb-positive sera, IgG1 isotype was detected in 90% SCA-POI and non-POI AAD sera and 67% APS1 patients. IgG1 isotype was found in 69% 17OHAb-positive SCA-POI and 100% 17OHAb-positive APS1 sera, and in 60% P450sccAb-positive SCA-POI and 80% P450sccAb-positive APS1 sera. For 21OHAb, IgG4 isotype was detected in 17% SCA-POI, 7% non-POI AAD, and 8% APS1 sera. None of the 17OHAb-positive sera was positive for IgG4. In P450sccAb-positive sera, 15% POI and 20% APS1 sera were positive for IgG4. Two 21OHAb-positive SCA-POI (7%), one 21OHAb-positive AAD (3%), three P450sccAb-positive SCA-POI (15%), and two P450sccAb-positive APS1 (20%) sera were positive for IgG4, in the absence of IgG1. All preclinical AAD sera resulted as positive for IgG1-21OHAb, but not for IgG4-21OHAb. Conclusions: The autoantibody responses in POI and AAD are IgG1 dominated, which suggests a predominant Th1 response. Selective IgG4 isotype specificity identified a small subset of patients with Th2-oriented response.

European Journal of Clinical Microbiology & Infectious Diseases, Mar 1, 2006

Reported here are the features of a Rhodotorula mucilaginosa outbreak that occurred in a neonatal... more Reported here are the features of a Rhodotorula mucilaginosa outbreak that occurred in a neonatal intensive care unit. Over a period of 19 days, clinical and laboratory signs of sepsis appeared in four premature infants carrying indwelling vascular catheters. After bloodstream infection with R. mucilaginosa was ascertained, the patients underwent amphotericin B therapy and recovered completely. In a retrospective case-control study, the variables displaying a statistical difference between case and control-group neonates were birth weight, gestational age, duration of parenteral nutrition, duration of antibiotic therapy and prophylactic administration of fluconazole. To our knowledge, this is the first reported outbreak caused by yeasts of the Rhodotorula genus.

Biochimica Et Biophysica Acta: Molecular Basis Of Disease, Feb 1, 2014

The Journal of Clinical Endocrinology and Metabolism, Feb 1, 2002

The Journal of Clinical Endocrinology and Metabolism, Nov 1, 2008

In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator g... more In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against type I interferons in 100% of Finnish and Norwegian patients, mainly with two prevalent AIRE truncations. Objectives: Because variability in clinical features and age at onset in APS-I frequently results in unusual presentations, we prospectively checked the diagnostic potential of anti-interferon antibodies in additional APS-I panels with other truncations or rare missense mutations and in disease controls with chronic mucocutaneous candidiasis (CMC) but without either common AIRE mutation. Design: The study was designed to detect autoantibodies against interferon-␣2 and interferonin antiviral neutralization assays. Setting and Patients: Patients included 14 British/Irish, 15 Sardinian, and 10 Southern Italian AIREmutant patients with APS-I; also 19 other patients with CMC, including four families with cosegregating thyroid autoimmunity. Outcome: The diagnostic value of anti-interferon autoantibodies was assessed. Results: We found antibodies against interferon-␣2 and/or interferon-in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British/Irish CMC patients. Especially against interferon-, titers were nearly always high, regardless of the exact APS-I phenotype/duration or AIRE genotype, including 12 different AIRE length variants or 10 point substitutions overall (n ϭ 174 total). Strikingly, in one family with few typical APS-I features, these antibodies cosegregated over three generations with autoimmune hypothyroidism plus a dominant-negative G228W AIRE substitution. Conclusions: Otherwise restricted to patients with thymoma and/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.

Frontiers in Immunology, Feb 12, 2018

About two decades ago, cloning of the autoimmune regulator (AIRE) gene materialized one of the mo... more About two decades ago, cloning of the autoimmune regulator (AIRE) gene materialized one of the most important actors on the scene of self-tolerance. Thymic transcription of genes encoding tissue-specific antigens (ts-ags) is activated by AIRE protein and embodies the essence of thymic self-representation. Pathogenic AIRE variants cause the autoimmune polyglandular syndrome type 1, which is a rare and complex disease that is gaining attention in research on autoimmunity. The animal models of disease, although not identically reproducing the human picture, supply fundamental information on mechanisms and extent of AIRE action: thanks to its multidomain structure, AIRE localizes to chromatin enclosing the target genes, binds to histones, and offers an anchorage to multimolecular complexes involved in initiation and post-initiation events of gene transcription. In addition, AIRE enhances mRNA diversity by favoring alternative mRNA splicing. Once synthesized, ts-ags are presented to, and cause deletion of the self-reactive thymocyte clones. However, AIRE function is not restricted to the activation of gene transcription. AIRE would control presentation and transfer of self-antigens for thymic cellular interplay: such mechanism is aimed at increasing the likelihood of engagement of the thymocytes that carry the corresponding T-cell receptors. Another fundamental role of AIRE in promoting self-tolerance is related to the development of thymocyte anergy, as thymic self-representation shapes at the same time the repertoire of regulatory T cells. Finally, AIRE seems to replicate its action in the secondary lymphoid organs, albeit the cell lineage detaining such property has not been fully characterized. Delineation of AIRE functions adds interesting data to the knowledge of the mechanisms of self-tolerance and introduces exciting perspectives of therapeutic interventions against the related diseases.

The Journal of Clinical Endocrinology and Metabolism, Mar 1, 2007

Context: Aromatic L-amino acid decarboxylase (AADC) is target of autoantibodies in autoimmune pol... more Context: Aromatic L-amino acid decarboxylase (AADC) is target of autoantibodies in autoimmune polyendocrine syndrome I (APS I), especially in patients with autoimmune hepatitis. Little information is currently available on AADC autoantibody epitopes and on the interrelation between autoantibody-mediated inhibition of enzymatic activity and epitope specificity. Design: We tested the immunoreactivity of full-length porcine AADC and of eight fragments of the enzyme with human serum from 18 patients with APS I, 199 with non-APS I autoimmune Addison's disease, 124 with type 1 diabetes mellitus, 36 with Graves' disease, and 141 healthy control subjects, and we evaluated the autoantibodymediated enzymatic inhibition. Results: AADC antibodies (Ab) were detected in 12 of 18 (67%) APS I patients and in six of 199 (3%) autoimmune Addison's disease patients. Four patients with autoimmune hepatitis were all positive for AADCAb. None of the 141 healthy control subjects, 82 patients with nonautoimmune adrenal insufficiency, 124 with type 1 diabetes mellitus, and 36 with Graves' disease were found positive. Two epitope regions, corresponding to amino acids 274-299 (E1) and 380-471 (E2) were identified. Localization of E1 was confirmed by displacement studies with synthetic peptides corresponding to peptides of porcine AADC. All 12 AADCAb-positive APS I sera reacted with E1, and seven of 12 (58%) reacted also with E2. E2-specific, but not E1-specific, autoantibodies were associated with a significant inhibition of in vitro AADC enzymatic activity. Conclusions: We mapped the human AADCAb epitopes to the middle and COOH-terminal regions of the enzyme. Autoantibodies to the COOH-terminal region induce a significant inhibition of enzymatic activity.

Italian journal of gastroenterology and hepatology, 1997

Microbiologia Medica, 2003

Scopo dello studio, tuttora in corso, è quello di determinare la sensibilità al "Fluconazolo" di ... more Scopo dello studio, tuttora in corso, è quello di determinare la sensibilità al "Fluconazolo" di diversi ceppi di Candida, scelti con l'intento di valutare un campione di popolazione che sia il più possibile ampio per numero di specie e per sede di isolamento. Questo antifungino tiazolico, infatti, viene utilizzato nel primo approccio terapeutico di candidiasi diverse per sede e specie coinvolta più spesso di altri; ciò sia per considerazioni di natura economica, sia per alcune favorevoli caratteristiche relative alla farmacocinetica ed alla bassa tossicità del Fluconazolo, che ne rendono la gestione più agevole rispetto ad altri antimicotici,. Il metodo utilizzato è l'ETEST AB BIODISK che, per la sua buona riproducibilità e la semplicità di allestimento, risulta applicabile routinariamente rispetto ai più elaborati metodi di diluizione in brodo (NCCLS M27-A) da cui derivano i breakpoint interpretativi per diverse specie di Candida. Tuttavia, nei casi di MIC > 16 g/ml, è stata verificata la concordanza dei risultati dell'Etest rispetto a quelli ottenuti con il metodo delle microdiluizioni (MDB). Materiali e metodi. 132 ceppi appartenenti alle specie indicate in Tabella 1, identificati con il sistema ID32C Biomerieux sono stati isolati da 18 emocolture, 5 cateteri venosi, 39 espettorati, 7 broncoaspirati, 18 tamponi faringei, 19 tamponi vaginali, 10 cateteri vescicali, 12 drenaggi o tamponi da ferite chirurgiche, 4 colture di bile. Da tutti i ceppi, utilizzando inoculi pari a 0.5 McFarland ottenuti da colture di 24h, sono stati allestiti gli Etest su Agar Casitone modificato e su Sabouraud Destrosio Agar, incubando per 24 h a 35°C. La concordanza Etest-MDB è stata valutata in 26 ceppi (Tabella 2) con MIC > 16 g/ml, da cui sono stati allestiti inoculi in piastre Microtiter in cui erano state preparate microdiluizioni di Fluconazolo in RPMI 1640 (secondo NCCLS M27-A),.