Chilblain lupus erythematosus is a rare form of cutaneous lupus erythematosus characterized by bluish red infiltrates in acral locations of the body mostly affecting middle-aged women. We recently described a familial form of chilblain lupus manifesting in early childhood caused by a heterozygous mutation in the TREX1 gene, which encodes a 3′-5′ DNA exonuclease. Thus, familial chilblain lupus represents the first monogenic form of cutaneous lupus erythematosus. Here we describe the unusual clinical course of this newly defined genodermatosis in an 18-year-old female member of the family in which familial chilblain lupus was originally described. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Patients were selected for the study on the basis of 1: A diagnosis of systemic Lupus Erythematosus according to the 1982 revised American Rheumatology Association criteria47 and 2: An adequate biopsy defined as containing at least six glomeruli. Patients were biopsied at Groote Schuur Hospital during the period 1978 to 1988 and the indications for renal biopsy were clinical based on laboratory results of renal function. Patients were followed between 1 and 120 months with a mean observation period of 34 months. The clinical records were scrutinised and the following pa·rameters were noted at the time of biopsy: age, sex, race, time from diagnosis to biopsy, serum urea, creatinine, creatinine clearence and urinary 24 hour protein. Using the latest serum urea, creatinine, creatinine clearence and / or 24 hour urinary protein where available, outcome was graded as: 1: An improvement in renal function 2: A stable renal function 3: Deterioration in renal function 4: Patient on dialysis 5: Death due to disease.

The major pathologic feature of the human autoimmune disease Systemic Lupus Erythematosus (SLE) and its murine counterpart, murine lupus, is the production of autoantibodies to nucleic acid antigens. In this study, a panel of six murine monoclonal anti-DNA autoantibodies was characterized at both the cellular and molecular levels in order to determine their possible role in the etiology of autoimmune disease. At the cellular level the autoantibodies were found to be highly cross-reactive, binding to three different antigenic forms of DNA as well as to the cell surface of various lymphoid cell lines. Furthermore, the fact that this autoantibody binding could be abrogated by pretreating the cells with either Proteinase K or DNase supports the hypothesis that a DNA binding protein may exist on the cell surface and that DNA bound to this receptor may serve as the target for the anti-DNA autoantibody. At the molecular level, the immunoglobulin (Ig) gene segments (V(H), D, J(H)) used to encode the variable region of the heavy chain of an anti-DNA autoantibody were sequenced. All three gene segments could be identified as members of established Ig gene segment families. In fact, the heavy chain of an antibody directed against the hapten L-glutamine₆₀-L-alanine₃₀-L-tyrosine₁₀ polymer (GAT) was found to utilize the same combination of V(H), D, and J(H) gene segments as the anti-DNA autoantibody. These results clearly indicate that autoantibodies are encoded by gene segments from the same Ig gene families used to encode antibodies to exogenous antigens. However, the discovery that this anti-DNA autoantibody is encoded by the same V(H) gene segment which encodes another anti-DNA autoantibody, derived from a different autoimmune mouse strain, supports the idea that certain V(H) gene segments may, in fact, be preferentially used to encode autoantibodies.

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A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Master of Science in Medicine. Johannesburg, June 2017 / Introduction: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease of unknown aetiology. There is growing evidence environmental factor(s) trigger the disease in the genetically susceptible host. Fragment crystallisable receptor (FCR) genes encode receptors that recognise the fragment crystallisable (Fc) portion of immunoglobulins (IgG) play an important role in the removal of antigen-antibody complexes from the circulation. Genes that code for these receptors have shown to be associated with susceptibility to SLE in various populations. The aim of the present study is to determine the role of single nucleotide polymorphisms (SNPs), allotypes and copy number variations of FC Gamma receptor genes IIIA and IIIB in susceptibility for the Black South Africans with SLE. Methods: DNA from 162 Black South African SLE patients and 155 matched controls were investigated using Taqman assays to determine SNP genotyping differences (FCGRIIIA) and copy number variation (CNV) number (FCGRIIIB). A PCR was optimised in order to determine the allotype differences (FCGRIIIB) via agarose gel electrophoresis. Statistical analyses were then performed on the data to see if the results displayed significance in susceptibility to SLE. Results: The minor allele of the allotypes (FCGRIIIB) and the rs396991 SNP (FCGRIIIA) were not statistically significant in conferring susceptibility to SLE in cases or controls. The rs10127393 SNP (FCGRIIIA) was shown to be monomorphic within both cases and controls for the T allele and is not associated with SLE. The cumulative percentage of copy numbers (FCGRIIIB) ≤2 copies were 0.6% larger in cases than seen in controls. Although this was not significant, this was what has been previously suggested in the literature. Almost half of the cases (43.8%) had lupus nephritis (LN). Upon investigation the NA1/NA2 alleles were found to confer susceptibility to LN (p=0.018), whereas the rs396991 G allele did not (p=0.643). Conclusion: In this study the allotypes, SNPs and CNV investigated were not found to confer susceptibility to SLE. However, subtle trends suggest that further studies are required with larger sample sizes to acquire more data. Almost half of the cases were diagnosed with LN and the NA2 allele was shown to be a risk factor in developing LN. / MT2017

ABSTRACT OBJECTIVE: To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti- β2-glycoprotein 1 (aβ2GP1) and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE) METHODS: A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, aβ2GP, and aPT of all isotypes, and LA. RESULTS: Positive aCL, aβ2GP1 and aPT and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG aβ2GP1 were the commonest aCL (49.1%) and aβ2GP1 (47%) isotypes, respectively. IgA aβ2GP1 were associated with both a history of thrombosis alone (p<0.05) and a history of any clinical feature, thrombosis and/or spontaneous abortion of the APS (p<0.05); IgA aCL were associated with a history of any clinical APS event (p<0.05); and aβ2GPI of any isotype were associated with a history of arthritis (p<0.001). CONCLUSION: My findings provide further evidence that the screening for aβ2GP1 and IgA aCL isotype may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for increased IgA aPL response in SLE patients of African extraction.

Faculty of Health School of Medicine 9101327d swadee@xsinet.co.za / Little is known about the epidemiological and mortality patterns of systemic lupus erythematosus (SLE) in Africa. Aims of this study- to determine the demographics, clinical features and causes and predictors death in patients attending the Lupus clinic at the Chris Hani Baragwanath hospital in Soweto. Methods- the records of 226 patients who fulfilled American College of Rheumatism criteria for the diagnosis of SLE were reviewed. The mean (± SD) age at presentation was 34 (± 12.5) years. The female to male ratio was 18:1. The commonest clinical feature found was arthritis in 70.4% of patients. Nephritis was present in 43.8% and CNS lupus in 15.9% of patients. 55 patients in this group had died and 64 were lost to follow up. The 5-year survival was 57% uncensored and 72% if censored for loss to follow up. Infection (32.7%) was the commonest cause of death followed by renal failure (16.4%). Nephritis, CNS lupus and hypocomplementaemia were associated with mortality on univariate analysis. Lupus nephritis was the only independant predictor of mortality on multivariate analysis. Conclusion- this study confirms the poor outcome of SLE in the developing world and demonstrates that renal disease is a factor commonly implicated in mortality. The 5-year survival and pattern of mortality is similar to that reported elsewhere in the developing world

Introdução: lúpus eritematoso é uma doença crônica auto-imune que afeta o tecido conjuntivo e múltiplos órgãos. Manifestações orais são pouco freqüentes, caracterizadas por lesões de aspectos variados. Diagnósticos diferenciais incluem líquen plano, leucoplasia, eritema polimorfo e pênfigo vulgar. Métodos: O objetivo deste trabalho foi estudar as lesões orais de 46 doentes com LE do ambulatório de Colagenoses e de Estomatologia do HC-FMUSP, enfocando os aspectos clínicos, histológicos, a proliferação e maturação epitelial (expressão de citoqueratinas, p-53 e ki-67), as proteínas da membrana basal (colágeno IV, fibronectina e laminina) e a constituição do infiltrado inflamatório (anticorpos CD3, CD4, CD8, CD 20, CD 68 e CD1A). Resultados: Quarenta e seis doentes (34 mulheres e 12 homens) apresentaram lesões orais, todos com alterações histológicas de mucosite de interface, infiltrado inflamatório superficial e profundo e depósitos subepiteliais PAS positivos. Positividade para IgM ao longo da membrana basal do epitélio foi observada pelo exame de IFD na maioria dos doentes. A avaliação das citoqueratinas mostrou um epitélio hiperproliferativo com expressão de CK 5/6 e CK 14 em todas as camadas, além da marcação do p-53 e ki-67 na camada basal. Os linfócitos T subtipo CD4 predominaram no infiltrado inflamatório, sendo mais rara a presença de linfócitos B e macrófagos. Células de Langerhans foram ausentes. Colágeno IV mostrou intensa expressão na membrana basal, a expressão da fibronectina foi mais difusa na lâmina própria e não se observou a presença de laminina. Conclusão: as lesões orais do LE predominam no sexo feminino e exibem aspectos clínicos variados. A mucosa jugal e lábios foram mais afetados. O aspecto histológico foi o de mucosite de interface associada a infiltrado inflamatório superficial e profundo com predomínio de linfócitos T CD4+, As citoqueratinas mostraram alteração no padrão de distribuição, caracterizando um epitélio hiperproliferativo. Na matriz extracelular predominou o colágeno IV na membrana basal. / Background: Lupus erythematosus (LE) is a multifactorial autoimmune disease of unknown cause. It may affect the oral mucosa in either its acute, subacute and chronic forms, with varied prevalence. Reports evaluate that mucosal involvement ranges from 9-45% in patients with systemic disease and from 3-20% in patients with chronic cutaneous involvement. Methods: Forty-six patients with confirmed diagnosis of LE, presenting oral lesions were included in the study. Oral mucosal lesions were analyzed clinically and their histopathological features were investigated. Additionally, using immunohistochemistry, the status of epithelial maturation proliferation and apoptosis of the biopsied lesions was assessed through the expression of cytokeratins, ki-67 and Fas. The inflammatory infiltrate constitution was also assessed using immunohistochemistry against the following clusters of differentiation: CD3, CD4, CD8, CD20, CD68 and CD1A. Finally, the components of extracellular matrix were analyzed trough the expression of collagen, laminin and fibronectina. Results: From 46 (15,45%) patients with specific LE oral lesions 34 were females (25) with cutaneous LE and 9 with systemic LE) and 12 were males (11 with cutaneous LE and 1 with systemic LE) out of 298 patients examined with lupus erithematosus. Clinical aspects of lesions varied, and lips and buccal mucosa were the most affected sites. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement membrane. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6 and CK14 on all epithelial layers, CK16 on all suprabasal layers. CK10 was verified on the prickle cell layer only. Ki-67 and p53 were sparsely positive and Fas was present both in the basal layer of the epithelium and in the inflammatory infiltrate. Inflammatory infiltrate was predominantly composed by T lymphocytes of the CD4 subtype, with a minor prevalence of Blymphocytes, isolated macrophages and rare Langerhans cells. Matrix proteins collagen IV and laminin were present mainly in the basement membranes of the epithelium and blood vessels, whilst fibronectina was not detected. Conclusions: Oral lesions of lupus erythematosus show a variety of clinical aspects and histologically consist of a lichenoid mucositis with deep inflammatory infiltrate. Patterns of cytokeratins expression are of a hyperproliferative epithelium and the inflammatory infiltrate is composed predominantly of T-lymphocytes positive lymphocytes. This panel must analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease.