Suzanne Wilhelmus - Academia.edu (original) (raw)
Uploads
Papers by Suzanne Wilhelmus
Journal of the American Society of Nephrology : JASN, Jan 7, 2015
Over 10 years have passed since the latest revision of the histopathologic classification of lupu... more Over 10 years have passed since the latest revision of the histopathologic classification of lupus nephritis. This revision was a significant improvement compared with the previous version, mainly because of clearer and more concise definitions and the elimination of mixed subclasses. Despite these improvements, there are still some difficulties in the classification for lupus nephritis, many of which are in the definitions provided. In this review, we focus on the difficulties surrounding the evaluation of classes III and IV lesions, particularly the definitions of endocapillary and extracapillary proliferation, the use of the terms endocapillary proliferation and hypercellularity, the clinical relevance of segmental and global subdivision in class IV, and the value of distinguishing lesions that indicate activity and chronicity. Vascular and tubulointerstitial lesions are also discussed. Furthermore, we give an overview of the history of the classification to provide background on...
Nephrology Dialysis Transplantation, 2015
Keywords (max 5): systemic lupus erythematosus, lupus nephritis, treatment, guideline, management... more Keywords (max 5): systemic lupus erythematosus, lupus nephritis, treatment, guideline, management Word count manuscript (including abstract, excluding tables): 3793 Number of tables: 3 Number of supplemental tables: 3 Number of references: 55
Journal of the American Society of Nephrology : JASN, Jan 8, 2015
Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can o... more Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can occur in a variety of clinical conditions. Promising results of recent trials with terminal complement-inhibiting drugs call for biomarkers identifying patients who might benefit from this treatment. The primary aim of this study was to determine the prevalence and localization of complement factor C4d in kidneys of patients with TMA. The secondary aims were to determine which complement pathways lead to C4d deposition and to determine whether complement activation results in deposition of the terminal complement complex. We examined 42 renal sections with histologically confirmed TMA obtained from a heterogeneous patient group. Deposits of C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were scored in the glomeruli, peritubular capillaries, and arterioles. Notably, C4d deposits were present in 88.1% of TMA cases, and the various clinical conditions had distinct staining patterns within ...
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2015
To treat lupus nephritis effectively, proper identification of the histologic class is essential.... more To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined. A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, κ or intraclass correlation values were calculated. The intraclass correlation or κ-value was also calculated for two separate levels...
Hypertension, 2013
Preeclampsia is associated with increased levels of the circulating antiangiogenic factor sFlt-1 ... more Preeclampsia is associated with increased levels of the circulating antiangiogenic factor sFlt-1 and with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can, therefore, contribute to the systemic manifestations of preeclampsia. In this study, we measured placental soluble fms-like tyrosine kinase-1 (sFlt-1) mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic and control subjects. To confirm the placental origin of these aggregates in maternal lungs, immunohistochemistry for the placenta-specific marker hCG (human chorionic ghonadotropin) and Y chromosome in situ hybridization were performed. Using human placental tissue, we found that syncytial knots are the principal site of expression of the antiangiogenic factor sFlt-1. In addition, autopsy material obtained from women with preeclampsia (n=9) showed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n=26). Importantly, these aggregates still contained the antiangiogenic factor sFlt-1 after their entrapment in the maternal lungs. The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. In addition, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia.
Microchimerism is the occurrence of small populations of cells with a different genetic backgroun... more Microchimerism is the occurrence of small populations of cells with a different genetic background within an individual. Tissue microchimerism is considered to be primarily pregnancy-derived and is often studied relative to female-dominant autoimmune diseases, pregnancy complications, malignancies, response to injury, and transplantation outcomes. A particular distribution pattern of chimeric cells across various organs was recently described in a model of murine pregnancies. Our aim was to determine the frequency and distribution of tissue micro-chimerism across organs during and after pregnancy in humans. We performed in situ hybridization of the Y chromosome on paraffin-embedded autopsy samples of kidneys, livers, spleens, lungs, hearts and brains that were collected from 26 women who died while pregnant or within 1 month after delivery of a son. Frequencies of chimeric cells in various tissues were compared with those of a control group of non-pregnant women who had delivered sons. Tissue microchimerism occurred significantly more frequently in the lungs, spleens, livers, kidneys and hearts of pregnant women compared with non-pregnant women (all P , 0.01). We showed that some of the chimeric cells were CD3+ or CD34+. After correction for cell density, the lung was most chimeric (470 Y chromosome-positive nuclei per million nuclei scored), followed by the spleen (208 Y+/ 10 6 nuclei), liver (192 Y+/10 6 nuclei), kidney (135 Y+/10 6 nuclei), brain (85 Y+/10 6 nuclei) and heart (40 Y+/10 6 nuclei). Data from this unique study group of women who died while pregnant or shortly after delivery provide information about the number and physiologic distribution of chimeric cells in organs of pregnant women. We demonstrate that during pregnancy, a boost of chimeric cells is observed in women, with a distribution across organs, that parallels findings in mouse models.
Journal of the American Society of Nephrology : JASN, Jan 7, 2015
Over 10 years have passed since the latest revision of the histopathologic classification of lupu... more Over 10 years have passed since the latest revision of the histopathologic classification of lupus nephritis. This revision was a significant improvement compared with the previous version, mainly because of clearer and more concise definitions and the elimination of mixed subclasses. Despite these improvements, there are still some difficulties in the classification for lupus nephritis, many of which are in the definitions provided. In this review, we focus on the difficulties surrounding the evaluation of classes III and IV lesions, particularly the definitions of endocapillary and extracapillary proliferation, the use of the terms endocapillary proliferation and hypercellularity, the clinical relevance of segmental and global subdivision in class IV, and the value of distinguishing lesions that indicate activity and chronicity. Vascular and tubulointerstitial lesions are also discussed. Furthermore, we give an overview of the history of the classification to provide background on...
Nephrology Dialysis Transplantation, 2015
Keywords (max 5): systemic lupus erythematosus, lupus nephritis, treatment, guideline, management... more Keywords (max 5): systemic lupus erythematosus, lupus nephritis, treatment, guideline, management Word count manuscript (including abstract, excluding tables): 3793 Number of tables: 3 Number of supplemental tables: 3 Number of references: 55
Journal of the American Society of Nephrology : JASN, Jan 8, 2015
Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can o... more Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can occur in a variety of clinical conditions. Promising results of recent trials with terminal complement-inhibiting drugs call for biomarkers identifying patients who might benefit from this treatment. The primary aim of this study was to determine the prevalence and localization of complement factor C4d in kidneys of patients with TMA. The secondary aims were to determine which complement pathways lead to C4d deposition and to determine whether complement activation results in deposition of the terminal complement complex. We examined 42 renal sections with histologically confirmed TMA obtained from a heterogeneous patient group. Deposits of C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were scored in the glomeruli, peritubular capillaries, and arterioles. Notably, C4d deposits were present in 88.1% of TMA cases, and the various clinical conditions had distinct staining patterns within ...
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2015
To treat lupus nephritis effectively, proper identification of the histologic class is essential.... more To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined. A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, κ or intraclass correlation values were calculated. The intraclass correlation or κ-value was also calculated for two separate levels...
Hypertension, 2013
Preeclampsia is associated with increased levels of the circulating antiangiogenic factor sFlt-1 ... more Preeclampsia is associated with increased levels of the circulating antiangiogenic factor sFlt-1 and with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can, therefore, contribute to the systemic manifestations of preeclampsia. In this study, we measured placental soluble fms-like tyrosine kinase-1 (sFlt-1) mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic and control subjects. To confirm the placental origin of these aggregates in maternal lungs, immunohistochemistry for the placenta-specific marker hCG (human chorionic ghonadotropin) and Y chromosome in situ hybridization were performed. Using human placental tissue, we found that syncytial knots are the principal site of expression of the antiangiogenic factor sFlt-1. In addition, autopsy material obtained from women with preeclampsia (n=9) showed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n=26). Importantly, these aggregates still contained the antiangiogenic factor sFlt-1 after their entrapment in the maternal lungs. The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. In addition, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia.
Microchimerism is the occurrence of small populations of cells with a different genetic backgroun... more Microchimerism is the occurrence of small populations of cells with a different genetic background within an individual. Tissue microchimerism is considered to be primarily pregnancy-derived and is often studied relative to female-dominant autoimmune diseases, pregnancy complications, malignancies, response to injury, and transplantation outcomes. A particular distribution pattern of chimeric cells across various organs was recently described in a model of murine pregnancies. Our aim was to determine the frequency and distribution of tissue micro-chimerism across organs during and after pregnancy in humans. We performed in situ hybridization of the Y chromosome on paraffin-embedded autopsy samples of kidneys, livers, spleens, lungs, hearts and brains that were collected from 26 women who died while pregnant or within 1 month after delivery of a son. Frequencies of chimeric cells in various tissues were compared with those of a control group of non-pregnant women who had delivered sons. Tissue microchimerism occurred significantly more frequently in the lungs, spleens, livers, kidneys and hearts of pregnant women compared with non-pregnant women (all P , 0.01). We showed that some of the chimeric cells were CD3+ or CD34+. After correction for cell density, the lung was most chimeric (470 Y chromosome-positive nuclei per million nuclei scored), followed by the spleen (208 Y+/ 10 6 nuclei), liver (192 Y+/10 6 nuclei), kidney (135 Y+/10 6 nuclei), brain (85 Y+/10 6 nuclei) and heart (40 Y+/10 6 nuclei). Data from this unique study group of women who died while pregnant or shortly after delivery provide information about the number and physiologic distribution of chimeric cells in organs of pregnant women. We demonstrate that during pregnancy, a boost of chimeric cells is observed in women, with a distribution across organs, that parallels findings in mouse models.