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Abstract: Objective: The purpose of our study is to appreciate the prevalence of antibodies anti PM-Scl within the framework of antinuclear antibodies detection and to clarify clinical biological and evolutive features associated to these antibodies. Methods: 9747 consecutive antinuclear testing datas allowed us to evaluate anti PM-Scl antibodies frequency. A retrospective analysis of patients characteristics was performed to identify clinical, biological and evolutive signs associated with this antibody over a five years follow up period. Results: Over the 9747 samples tested for antinuclear antibodies detection, 3493 (35.8%) are positive. An anti ENA activity is observed in 727 (7.5%) cases and anti PM-Scl in 6 (0.06%). These antibodies are described in systemic sclerosis, myositis or overlap syndromes. All theses diseases showed a low evolutivity over the five years of follow up. Conclusions: Low prevalence and possible association with an overlap autoimmune syndrome of quite good prognosis are reported with anti PM-Scl antibodies. [Copyright &y& Elsevier]

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Introduction: Complement activation emerged as a key actor of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Whether serum levels of C3 (sC3) or C3 kidney deposition may help to refine the prognosis of AAV remains elusive., Methods: Retrospective multicentric study that included 154 patients with a first flare of AAV and sC3 (n = 143) or C3 kidney staining (n = 95) available at diagnosis. Clinical presentations, kidney pathology, and survival of patients with normal or low sC3 were compared using univariate analyses, Kaplan-Maier curves with log-rank comparison, or multivariate Cox' model, as appropriate., Results: 20 patients (14 %) had low sC3. sC3 (as bivariate low/normal or as a continuous variable) was associated with 5-year mortality but not with kidney survival. C3 kidney deposition (C3+) was identified in 23 patients who were characterized by more frequent chronic hypertension and lower eGFR at presentation (p = 0.04). C3+ correlated with IgG, IgM, C1q deposition (p = 0.07, p < 0.0001 and p = 0.003, respectively). Chronicity and activity scores were similar in C3+ and C3- patients. Among C3+ patients, those with C3 deposition ≥2+ had lower eGFR at presentation (p = 0.006) and were more frequently classified as sclerotic using the Berden classification (p = 0.04) and as 'high risk' using the Brix score (p = 0.03). However, eGFR improvement following induction regimen was similar between C3+ and C3- patients, and kidney survival at 5 years was similar., Conclusions: Correlation of sC3 with mortality confirms mechanistic links between complement pathways and AAV, but the lack of clear predictive sC3 cut-off and the similar kidney outcome irrespective of C3 deposition precludes their use as biomarkers of AAV outcomes and response to treatment., Competing Interests: SF received consulting fees from Abionyx Pharma and Novartis SA, fees for Scientific advisory board or lecture fees by CSL-Vifor, Sanofi-Genzyme, Alexion-AstraZeneca and Baxter. Other authors reported no conflict of interests., (© 2023 The Authors.)

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.

Objective: Because of its heterogeneity in clinical presentation and course, predicting autoimmune encephalitis (AIE) evolution remains challenging. Hence, our aim was to explore the correlation of several biomarkers with the clinical course of disease., Methods: Thirty-seven cases of AIE were selected retrospectively and divided into active ( N  = 9), improved ( N  = 12) and remission ( N  = 16) AIE according to their disease evolution. Nine proteins were tested in both serum and cerebrospinal fluid (CSF) at diagnosis (T0) and during the follow-up (T1), in particular activated MMP-9 (MMP-9A) and YKL-40 (or chitinase 3-like 1)., Results: From diagnosis to revaluation, AIE remission was associated with decreased YKL-40 and MMP-9A levels in the CSF, and with decreased NfL and NfH levels in the serum. The changes in YKL-40 concentrations in the CSF were associated with (1) still active AIE when increasing >10% ( P- value = 0.0093); (2) partial improvement or remission when the changes were between +9% and -20% ( P- value = 0.0173); and remission with a reduction > -20% (P- value = 0.0072; overall difference between the three groups: P- value = 0.0088). At T1, the CSF YKL-40 levels were significantly decreased between active and improved as well as improved and remission AIE groups but with no calculable threshold because of patient heterogeneity., Conclusion: The concentration of YKL-40, a cytokine-like proinflammatory protein produced by glial cells, is correlated in the CSF with the clinical course of AIE. Its introduction as a biomarker may assist in following disease activity and in evaluating therapeutic response., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Introduction: Guillain-Barré syndrome (GBS) is an acute post-infectious inflammatory polyneuropathy of ubiquitous distribution. Cytomegalovirus (CMV) is the virus that is most frequently involved. All ages are affected but rare pediatric cases seem to show some distinctive features in terms of specificity and severity. Specific antibodies that target the peripheral nervous system have been identified in several forms of GBS in adults, such as anti-GM2 ganglioside antibodies in post-CMV GBS, which in most instances present as demyelinating polyneuropathies, with a more favorable progression and fewer complications., Materials and Methods: This is a retrospective report on two cases of post-CMV GBS with a demyelinating disorder and positive for anti-GM2 IgM. The review of the literature examines five other cases of children with post-CMV GBS with anti-GM2 IgM., Results: In terms of progression, our two cases of post-CMV GBS with a demyelinating disorder and anti-GM2 IgM are similar to the five other cases described in the literature. The CMV infection was asymptomatic or paucisymptomatic and involved girls (6/7), often presenting severe motor forms with frequent loss of the ability to walk (4/6), facial involvement (⅗), little respiratory involvement (⅙), and favorable progression with adapted treatment., Conclusion: Post-CMV GBS with anti-GM2 IgM is a specific clinical spectrum that seems to affect children as it affects adults with a predominance among females, demyelination, and severe motor involvement, but a good prognosis. On the other hand, unlike adults, the use of assisted ventilation does not seem to be more frequent., Competing Interests: None declared., (Thieme. All rights reserved.)

The lupus band test (LBT) is frequently performed for patients with lupus erythematosus (LE) but its capacity to discriminate cutaneous (C)LE from systemic (S)LE is debated, as well as its association with serum antinuclear antibodies (ANA) and complement reduction. Among 158 patients, 56 received retrospectively a diagnosis of CLE, 37 have SLE and 65 other skin disorders. Considering 29 clinical, histopathologic, LBT, and serological parameters: 5 parameters were effective in distinguishing LE from other skin disorders (e.g. skin photosensitivity, LBT positivity, basal vacuolar changes, thickening of the basement membrane, and anti-SSA-60 kDa); and 8 parameters were able to separate SLE from CLE (e.g. arthritis, lupus nephritis, hematological manifestations, Raynaud/sicca manifestations, anti-chromatin, anti-dsDNA, and low levels of C3/4). A positive LBT was further determined to be associated with systemic manifestations when associated with anti-chromatin response and complement reduction in the profile of patients evolving to a systemic form of lupus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Systemic sclerosis (SSc) is associated, in nearly all patients, with autoantibodies (Ab). Accordingly, and in order to identify major (anti-CEN A/B and anti-Topo I) but also minor Abs, the usefulness of combining indirect immunofluorescence (IIF) on HEp-2 cells with an 11 multi-antigenic SSc immunodot was explored. 1689 samples tested at the request of clinicians, were evaluated retrospectively. The positivity rate was 28.8% and the diagnosis of SSc was supported for 232 samples. Two groups of Abs were considered: group 1, Abs (anti-CENP A/B, anti-Topo I) present at elevated levels in SSc patients; group 2, Abs for which the Ab specificity (odds ratio and/or positive predictive value) was improved by using IIF on HEp-2 cells (RNA-Polymerase III, fibrillarin, Th/T0, PM-Scl). Altogether, this study highlights the utility of combining IIF on HEp-2 cells with the SSc immunodot as the first line of an SSc Abs detection/SSc diagnostic strategy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Patients with autoimmune Addison's disease (AAD) can develop other autoimmune diseases. They often display autoantibodies other than anti-adrenal cortex autoantibodies (ACA) which could be of interest in predicting the development of other diseases such as type 1 diabetes (T1D). Among the well-established autoantibodies associated with T1D, anti-ZnT8 autoantibodies (ZnT8A) could be found in absence of anti-GADA and anti-IA2A. Thus, the aim of our study was to evaluate the prevalence of ZnT8A in a cohort of AAD patients. The presence of ZnT8A was studied in 36 patients (19 children and 17 adults) displaying ACA. ZnT8A were detected in both children and adults with an overall prevalence of 19%. The results also indicated that ZnT8A were associated with coexisting T1D in more than 70% of this population regardless of age. Even if the titer of ZnT8A for the one third of patients without T1D was low, they have to be followed due to the potential risk of developing T1D. ZnT8A in those cases could also be a marker of autoimmunity associated to the adrenal gland destruction in AAD. As ZnT8A screening has been included in the diagnostic investigation of T1D, it should also be incorporated in the autoantibodies screening panel of the AAD population., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Chronic HSV infection is a cause of chronic perineal ulcerations. We report a case of a chronic and refractory HSV infection revealing chronic lymphoid leukaemia., Patients and Methods: An 85-year-old woman with an 8-month history of chronic perineal ulcerations was referred to our dermatology department. She had no previous medical history of herpes infection. Skin biopsies ruled out carcinoma but were consistent with HSV infection. A local swab was positive for HSV2. Treatment with valaciclovir and intravenous acyclovir (ACV) at the recommended doses was ineffective. Laboratory tests revealed type-B chronic lymphoid leukaemia. Molecular biology studies confirmed the presence of ACV-resistant HSV via decreased thymidine kinase activity (stop codon: M183stop). Foscarnet was administered for a period of 3 weeks with almost complete healing of the ulcerations. Treatment was stopped prematurely due to acute renal insufficiency and the remaining lesions were treated using imiquimod cream. Valaciclovir was prescribed to prevent further episodes. The condition recurred a mere 11 months later., Discussion: The prevalence of ACV-resistant HSV is 0.32 % in immunocompetent patients and 3.5 % in immunocompromised patients. Insufficient dosing regimens or prolonged treatment with TK inhibitors result in the local selection of pre-existing mutant HSV viruses. Foscarnet, a DNA polymerase inhibitor, is the treatment of choice in HSV-resistant infections. ACV-resistant HSV is less virulent and replicates less, with reactivations being mainly due to wild-type HSV latent in the neural ganglia. Valaciclovir can be used as a preventive treatment. To our knowledge, this is the first case of ACV-resistant HSV infection revealing chronic lymphoid leukaemia., Conclusion: Chronic perineal ulcerations can be the first manifestation of immunodeficiency seen for example with haematological diseases. In the event of clinical resistance of an HSV infection to recommended thymidine kinase inhibitor regimens, the use of foscarnet should be considered., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: We developed and validated a kinetic microplate hemolytic assay (HA) to quantify classical and alternative complement activity in a single dilution of human plasma or serum., Methods: The assay is based on monitoring hemolysis of sensitized sheep (or uncoated rabbit) red blood cells by means of a 96-well microplate reader. The activity of the calibrator was evaluated by reference to 200 healthy adults. The conversion of 50% hemolysis time into a percentage of activity was obtained using a calibration curve plotted daily., Results: The linearity of the assay as well as interference (by hemolysis, bilrubinemia and lipemia) was assessed for classical pathway (CP). The within-day and the between-day precision was satisfactory regarding the performance of commercially available liposome immunoassay (LIA) and ELISA. Patients with hereditary or acquired complement deficiencies were detected (activity was measured <30%). We also provided a reference range obtained from 200 blood donors. The agreement of CP evaluated on samples from 48 patients was 94% with LIA and 87.5% with ELISA. The sensitivity of our assay was better than that of LIA, and the cost was lower than either LIA or ELISA. In addition, this assay was less time consuming than previously reported HAs., Conclusions: This assay allows the simultaneous measurement of 36 samples in duplicate per run of a 96-well plate. The use of a daily calibration curve allows standardization of the method and leads to good reproducibility. The same technique was also adapted for the quantification of alternative pathway (AP) activity.

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.

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.