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Background: Myelin oligodendrocytes glycoprotein (MOG) antibody-associated disease (MOGAD) represent 25% of pediatric acquired demyelinating syndrome (ADS); 40% of them may relapse, mimicking multiple sclerosis (MS), a recurrent and neurodegenerative ADS, which is MOG-Abs negative., Aims: To identify MOG antigenic immunological response differences between MOGAD, MS and control patients, and between relapsing versus non-relapsing subgroups of MOGAD., Methods: Three groups of patients were selected: MOGAD (n=12 among which 5 relapsing (MOGR) and 7 non-relapsing (MOGNR)), MS (n=10) and control patients (n=7). Peripheral blood mononuclear cells (PBMC) collected at the time of the first demyelinating event were cultured for 48 h with recombinant human (rh)-MOG protein (10 μg/ml) for a specific stimulation or without stimulation as a negative control. The T cells immunophenotypes were analyzed by flow cytometry. CD4 + T cells, T helper (Th) cells including Th1, Th2, and Th17 were analyzed by intracellular staining of cytokines. Regulatory T cells (T regs , Foxp3 + ), CD45RA - Foxp3 + T regs and subpopulation naive T regs (CD45RA + Foxp3 int ), effector T regs (CD45RA - Foxp3 high ) and non-suppressive T regs (CD45RA - Foxp3 int ) proportions were determined., Results: The mean onset age of each group, ranging from 9.9 to 13.8, and sex ratio, were similar between MOGR, MOGNR, MS and control patients as analyzed by one-way ANOVA and Chi-square test. When comparing unstimulated to rh-MOG stimulated T cells, a significant increase in the proportion of Th2 and Th17 cells was observed in MOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15 vs. 1.36 ± 0.43; Wilcoxon-test p = 0.03) but not in MOGR. CD4 + T regs were significantly increased in MOGNR (means: 3.51 ± 0.7 vs. 4.59 ± 1.33; Wilcoxon-test p = 0.046) while they decreased in MOGR. CD45RA - Foxp3 + T regs were significantly decreased in MOGR (means: 2.37 ± 0.23 vs. 1.99 ± 0.17; paired t-test p = 0.021), but not in MOGNR. MOGR showed the highest ratio of effector T regs /non suppressive-T regs, which was significantly higher than in MOGNR., Conclusions: Our findings suggest that CD4 + Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of T regs to rh-MOG in MOGNR, where CD4 + T regs increased, and in MOGR, where CD45RA - Foxp3 + T regs decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Horellou, de Chalus, Giorgi, Leroy, Chrétien, Hacein-Bey-Abina, Bourgeois, Mariette, Serguera, Le Grand and Deiva.)

Auto-antibodies to the ubiquitous enzyme type-2 transglutaminase (TG2) are a specific hallmark of celiac disease (CD), a widely diffused, multi-factorial disease, affecting genetically predisposed subjects. In CD an inflammatory response, at the intestinal level, is triggered by diet consumption of gluten-containing cereals. Intestinal mucosa displays various degrees of atrophy and hyperplasia, with consequent global intestinal dysfunction and other relevant extra-intestinal symptoms. Through deamidation of specific glutamines of gluten-derived gliadin peptides, TG2 strongly enhances gliadin immunogenicity. In addition, TG2 cross-linking activity may generate complexes between TG2 itself and gliadin peptides, and these complexes seem to cause the auto-immune response by means of an apten-carrier-like mechanism of antigen presentation. Anti-TG2 antibodies can be early detected in the intestinal mucosa of celiac patients and are also abundantly present into the serum, thus potentially reaching other organs and tissues by blood circulation. Recently, the possible pathogenetic role of auto-antibodies to TG2 in CD has been investigated. Here, we report an overview about the genesis of these antibodies, their specificity, their modulating ability toward TG2 enzymatic or non-enzymatic activities and their biological effects exerted by interacting with extracellular TG2 or with cell-surface TG2. We also discuss the auto-immune response occurring in CD against other TG members (i.e. type 3 and type 6) and analyze the occurrence of anti-TG2 antibodies in other auto-immune CD-related diseases. Data now available let us to suppose that, even if antibodies to TG2 do not represent the triggering molecules in CD, they could be important players in disease progression and manifestations.

The detection of human anti-estrogen receptor α antibodies (ERαABs) inducing estrogenic responses in MCF-7 mammary tumor cells suggests their implication in breast cancer emergence and/or evolution. A recent report revealing a correlation between the titer of such antibodies in sera from patients suffering from this disease and the percentage of proliferative cells in samples taken from their tumors supports this concept. Complementary evidence of the ability of ERαABs to interact with an epitope localized within the estradiol-binding core of ERα also argues in its favor. This epitope is indeed inserted in a regulatory platform implicated in ERα-initiated signal transduction pathways and transcriptions. According to some experimental observations, two auto-immune reactions may already be advocated to explain the emergence of ERαABs: one involving probably the idiotypic network to produce antibodies acting as estrogenic secretions and the other based on antibodies able to abrogate the action of a natural ERα inhibitor or to prevent the competitive inhibitory potency of released receptor degradation products able to entrap circulating estrogens and co-activators. All of this information, the aspect of which is mainly fundamental, may open new ways in the current tendency to combine immunological and endocrine approaches for the management of breast cancer., Competing Interests: The author declares no conflict of interest. As Honorary (retired) Professor, I failed to have access to any kind of financial support.

The association between endometriosis and autoimmune diseases is well known, however no acquired platelet function defect has been described so far. We describe the case of two patients with endometriosis associated with an antiplatelet glycoprotein VI (anti-GPVI) antibody. The two women with deep pelvic endometriosis associated with secondary infertility presented a mild bleeding tendency, a deficient platelet aggregation response to collagen, convulxin or CRP and a severe GPVI deficiency. Immunoblot revealed a combined FcRy deficiency but no indication of GPVI cleavage. In the first case, platelet count was normal and an anti-GPVI IgG was detected in plasma. A first corticosteroids administration normalized in vitro platelet functions but further administrations were unsuccessful. Three IVF attempts failed. Conservative laparoscopic surgery was carried out after antifibrinolytic treatment without bleeding. The second case presented with a history of moderate thrombocytopenia and a weak anti-GPVI in the context of infertility and autoimmune disease, the Sjögren syndrome resolved after corticosteroids and hydroxychloroquine treatment. Acquired GPVI deficiencies are rare. It would be useful to determine whether the association with endometriosis is coincidental or not by more systematic investigations. It does not seem that in these patients, GPVI deficiency is associated with an increased risk of bleeding. [ABSTRACT FROM AUTHOR]

The association between endometriosis and autoimmune diseases is well known, however no acquired platelet function defect has been described so far. We describe the case of two patients with endometriosis associated with an antiplatelet glycoprotein VI (anti-GPVI) antibody. The two women with deep pelvic endometriosis associated with secondary infertility presented a mild bleeding tendency, a deficient platelet aggregation response to collagen, convulxin or CRP and a severe GPVI deficiency. Immunoblot revealed a combined FcRγ deficiency but no indication of GPVI cleavage. In the first case, platelet count was normal and an anti-GPVI IgG was detected in plasma. A first corticosteroids administration normalized in vitro platelet functions but further administrations were unsuccessful. Three IVF attempts failed. Conservative laparoscopic surgery was carried out after antifibrinolytic treatment without bleeding. The second case presented with a history of moderate thrombocytopenia and a weak anti-GPVI in the context of infertility and autoimmune disease, the Sjögren syndrome resolved after corticosteroids and hydroxychloroquine treatment. Acquired GPVI deficiencies are rare. It would be useful to determine whether the association with endometriosis is coincidental or not by more systematic investigations. It does not seem that in these patients, GPVI deficiency is associated with an increased risk of bleeding.

Abstract: Sensorineural hearing loss may be due to an autoimmune mechanism. The mechanisms that could induce autoimmune inner ear damage are now better understood, but are not exclusive. Moreover, there is no specific immunologic test available for the diagnosis of autoimmune sensorineural hearing loss, which could also complicate the disease course of other autoimmune systemic diseases. Thus, the incidence of sensorineural autoimmune hearing loss is probably underestimated. The aim of this study was to review the experimental immunologic data in favour of an autoimmune mechanism in this subgroup of sensorineural hearing loss: humoral specific response against inner ear (autoantibodies against a transmembrane transporter) and also cellular response (against cochlin: one of the major proteins expressed in the inner ear). The aim of this review was also to focus on clinical and epidemiological human data that provide evidence for an autoimmune etiopathogeny of some sensorineural hearing loss. Therapeutic options such as immunosuppressive treatments (oral corticosteroids and other immunosuppressive drugs, such as methotrexate and anti-TNFα) are also discussed. [Copyright &y& Elsevier]

Abstract: Objectives: This study aimed at evaluating the screening of thyroïditis and coeliac disease, in a population of children and adolescents with type 1 diabetes, and at comparing the appearance of antibodies specific for these 2 diseases as a function of age. Patients and methods: The study included 370 children and adolescents, 179 girls and 191 boys, aged 13.8 ± 4.4 yr and with diabetes for 7.1 ± 3.8 yr. Auto-immune thyroïditis was screened using antimicrosomal and antithyroglobulin auto-antibodies, at a mean rhythm of 3 tests per patient (1 every 2 yr), associated with dosages of TSH and FT4. Coeliac disease was screened using antigliadin (± antiendomysium) auto-antibodies, at a mean rhythm of 2 tests per patient, and was confirmed by duodenojejunal biopsy. Antithyroïd auto-antibodies were correlated with age following the « censured data analysis » type approach. Results: Antithyroïd autoantibodies were found in 42 patients (11.4%), of whom 9 were treated for hypothyroïdism and 1 for Basedow disease, and coeliac disease autoantibodies were found in 9 patients (3.2% of tested patients). The cumulated frequency of antithyroïd auto-antibodies increased regularly with age and was significantly higher in girls, reaching 28% in girls and 12% in boys around 18 yr of age. As a consequence of this evolution, antithyroïd auto-antibodies were frequently found at the time of diagnosis of diabetes when it declared after 10 yr of age, while they often became positive secondarily when diabetes occurred before 10 yr of age. Coeliac disease specific auto-antibodies appeared much earlier and were found at the time of diagnosis of diabetes or at the first screening test. Conclusion: Antithyroïd autoantibodies are increasingly frequent with age in children with type 1 diabetes, and become very elevated in girls. The rhythm for screening should be adapted to this evolution of autoantibodies with age, which is very different between thyroïditis and coeliac disease. [Copyright &y& Elsevier]