Urinary soluble CD163 is useful as "liquid biopsy" marker in lupus nephritis at both diagnosis and follow-up to predict impending flares.

Lupus nephritis (LN) diagnosis and follow-up requires noninvasive biomarkers. Therefore, the added value of coupling the urinary soluble (s)CD163/creatinuria ratio with serological markers was evaluated in a real-world clinical practice. To this end, a monocentric and retrospective study was conducted in 139 SLE patients with biopsy-proven nephritis having an active LN (LN-A, n = 63 with a positive SLEDAI-renal score) or inactive (n = 76), as well as 98 non-renal SLE patients. The urinary sCD163/creatinuria ratio outperformed serological markers for predicting LN-A (AUC>0.972; p < 10-4 with a 100 % specificity threshold fixed at 320 ng/mmol), and for monitoring renal activity allowing prediction of impending flares and remissions in follow-up (AUC = 0.789, p < 10-4). LN-A patients with an elevated spot proteinuria/creatinuria ratio (p = 8 × 10-6) and sCD163/creatinuria ratio (p = 10-3) were at risk for developing end-stage kidney disease but sCD163/creatinuria ratio cannot substitute kidney biopsy to discriminate LN-A from other glomerulonephritis. Among serological markers (n = 14), anti-dsDNA and anti-C1q antibodies (Abs) (AUC>0.750 versus non-LN patients, and AUC>0.640 versus LN-IR patients) best predicted LN-A, and higher levels were retrieved in class III/IV proliferative LN-A. In multivariate logistic regression analysis, the urinary sCD163/creatinuria ratio remained the only statistically significant biomarker to predict LN-A (p < 0.001). In conclusion, and as compared to classical serological markers, the urinary sCD163/creatinuria ratio provides an additional parameter for monitoring LN patients.

Accuracy of Serological Screening for the Diagnosis of Celiac Disease in Type 1 Diabetes Children.

Background and Objectives: Patients with type 1 diabetes (T1D) are considered at high-risk for developing celiac disease (CD). The purpose of our study was to determine the prevalence of CD among children who were followed in our unit for T1D using the latest ESPGHAN guidelines, and avoiding intestinal biopsies in some of the children. Materials and Methods: We performed a prospective monocentric study, which included 663 T1D children between June 2014 and June 2016. We considered CD according to serological (tissue transglutaminase (TGAs) and endomysium antibodies) results. Children were included either at the time of T1D diagnosis or during their follow up. We looked for clinical and biochemical signs of CD, and for T1D characteristics. Results: The children's ages ranged from 11 months to 18 years. CD was confirmed in 32 out of 663 patients with T1D, with a prevalence of 4.8%. CD was excluded in 619 children and remained uncertain for 12 children, who had positive TGAs without the required criteria. We found that 95% of T1D children express HLA-DQ2 and/or -DQ8, which was 2.4 times higher than in the general population. Conclusions: An intestinal biopsy could be avoided to confirm CD in the majority of T1D children. Silent forms of CD are frequent and screening is recommended for all patients. Importantly, repeated TGA assessment is required in HLA genetically predisposed T1D patients, while it is unnecessary in the 5% who are HLA-DQ2 and -DQ8 negative.

Case Report: Presence of Anti-MAG in the CSF Can Be Associated With a Neurodegenerative Process With Frontal Involvement.

Background: Autoimmune encephalitis (AIE) is an increasingly broad nosological framework that may clinically mimic neurodegenerative diseases (NDDs). Cases Reported: We describe here the clinical, radiological, electrophysiological, and biological evolution of three patients. Two women aged 73 and 72 years and a 69-year-old man presented with complex cognitive and focal neurological symptoms and each had a predominant frontal dysexecutive involvement and an unexpectedly high titer of anti-MAG antibodies in the serum and cerebrospinal fluid (CSF). The question of an autoimmune cause was raised. After 2 years of follow-up and, for two of them, without improvement despite immunosuppressive treatments, diagnoses of NDD were eventually retained: post-radiation encephalopathy, progressive supranuclear palsy (PSP), and Alzheimer's disease. Conclusion: The presence of a high titer of anti-MAG antibodies may be found in NDD. It could reflect cerebral tissue damages, particularly in the case of significant frontal involvement. Atypical presentations may lead to a search for a paraneoplastic neurologic syndrome or AIE. However, the indirect immunofluorescence staining positivity on a monkey cerebellum section linked with anti-MAG antibodies should not lead to those diagnoses being retained.

Clinical association of mixed connective tissue disease and granulomatosis with polyangiitis: a case report and systematic screening of anti-U1RNP and anti-PR3 auto-antibody double positivity in ten European hospitals.

We report here the case of a 50-years-old man treated for mixed connective tissue disease (MCTD) positive for anti-U1 ribonucleoprotein (U1RNP) antibodies who secondarily developed a granulomatosis with polyangiitis (GPA) associated with anti-proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA). We then evaluated the frequency of the association between anti-U1RNP and anti-PR3-ANCA antibodies by a systematic retrospective study in ten European hospitals. Overall, out of 11,921 samples analyzed for both auto-antibodies, 18 cases of anti-U1RNP and anti-PR3-ANCA double positivity were found and only one patient presented with both MCTD and GPA symptoms. Our retrospective analysis indicates that anti-U1RNP and anti-PR3-ANCA antibodies double positivity is infrequent and very rarely associated with both MTCD and GPA. Our observation describes for the first time the coexistence of MTCD and severe GPA in a Caucasian patient. Association of anti-U1RNP and ANCA antibodies was rarely reported in the literature. Eleven cases of MCTD and ANCA vasculitis have been reported to date, with only two cases with anti-PR3-ANCA association, and only one vasculitis. The seven other cases reported in the literature presented with an association of MCTD and microscopic polyangiitis which appears to be a more frequent presentation than MTCD associated with GPA.

Heterogeneous clinical spectrum of anti-SRP myositis and importance of the methods of detection of anti-SRP autoantibodies: a multicentric study.

Anti-signal recognition particle (SRP) antibodies are important serological markers for the diagnosis and the prognosis of idiopathic inflammatory myopathy (IIM), especially to distinguish immune-mediated necrotizing myopathy (IMNM). This study was set up to investigate the phenotype associated with anti-SRP antibodies and to evaluate the methods for detecting these antibodies. Clinical and biological data were retrospectively obtained from 60 adult patients with anti-SRP antibodies detected by a dot immunoassay from 12 centers. Thirty-six (60 %) out of these 60 patients suffered from an IIM, and among them, 21 patients were diagnosed as IMNM. Among patients with a definite IIM, proximal weakness and myalgia were prominent symptoms at the time of diagnosis. Only few patients displayed severe extra-muscular symptoms such as cardiac involvement or severe myositis. Mean creatine kinase levels were high for all patients except for two of them. When testing by indirect immunofluorescence (IIF) on HEp2 cells, the fraction of patients displaying the typical anti-SRP fine speckled staining of the cytoplasm was higher in patients with IIM (30/36) (83 %) than in patients with non-IIM (3/24) (12.5 %) (p < 0.0001). Thirty (91 %) out of 33 patients with a positive immunodot and a characteristic IIF cytoplasmic staining suffered from a clinical definite myositis, whereas only 6 (22 %) out of 27 patients with a positive immunodot but a negative cytoplasmic pattern suffered from a myositis (p < 0.00001). This series highlights the strong heterogeneity of anti-SRP positivity that encompassed IMNM and non-IMNM and supports the necessity of considering both IIF and dot immunoassay to confirm the diagnosis of anti-SRP-associated myositis.

Are immunoglobulin A anti-gliadin antibodies helpful in diagnosing coeliac disease in children younger than 2 years?

The usefulness of immumoglobulin (Ig) A antibodies to gliadin (AGA-IgA) in addition to IgA anti-endomysium and tissue transglutaminase antibodies was evaluated in 4122 children younger than 2 years with a suspicion of coeliac disease (CD). Eight percent (312/4122) displayed IgA anti-endomysium and/or IgA anti-tissue transglutaminase, whereas 2.1% (85/4122) displayed only AGA-IgA. Clinical data were obtained for 62 of 85 children with isolated AGA-IgA, and 33 children underwent a duodenal biopsy. Histologically proven CD was established for 5 patients, whereas 57 children were diagnosed to experience other diseases. The systematic detection of AGA-IgA using native gliadin conferred no additional diagnostic benefit for the diagnosis of CD in children younger than 2 years of age, except for rare cases.

IgA-mediated anti-glomerular basement membrane disease: an uncommon mechanism of Goodpasture's syndrome.

Goodpasture's (GP) disease is usually mediated by IgG autoantibodies. We describe a case of IgA-mediated GP, in a patient presenting with isolated rapidly progressive glomerulonephritis. The diagnosis was established on kidney biopsy, since routine enzyme-linked immunosorbent assay (ELISA) targeted at IgG circulating autoantibodies failed to detect the nephritogenic antibodies. Immunofluorescence microscopy showed intense linear deposition of IgA along the glomerular capillary walls. An elevated titre (1:80) of circulating IgA anti-glomerular basement membrane (GBM) antibodies was retrospectively demonstrated by indirect fluorescence. Despite immunosuppressive regimen, the disease progressed to end-stage renal failure (ESRF). Transplantation was not associated with recurrence in the kidney graft. We reviewed the 11 previously reported cases of IgA-mediated GP.