Welcome to the Autoimmunity 2021 Congress Calendar

Background and Aims

IgG4 autoimmune diseases are characterized by the presence of antigen-specific autoantibodies of IgG4 subclass, and contain well-characterised diseases such as MuSK myasthenia gravis, pemphigus and thrombotic thrombocytopenic purpura. Recently several new diseases were identified, and by now at least 21 antigens associated with IgG4 subclass are known. The IgG4 subclass is considered as immunologically inert and functionally monovalent The pathogenicity of IgG4 autoantibodies can be validated using our recently published classification system.

Methods

Using literature research, autoimmune diseases associated with IgG4 autoantibodies were identified. Clinical and immunological research data of identified diseases were critically reflected and the pathogenicity of the IgG4 autoantibodies was analysed using the classification system for IgG4 autoantibodies.

Results

As a result, one new class II and six new class III IgG4 autoimmune diseases were identified. New research data allowed a re-classification of Neurofascin-155 antibody associated CIDP as class I IgG4 autoimmune disease. IgG4 autoimmune diseases were found to be restricted to four distinct organs: 1) the central and peripheral nervous system, 2) the kidney, 3) the skin and mucous membranes and 4) the vascular system or soluble antigens in the blood circulation.

Conclusions

In conclusion, there are to date six class I (verified), five class II (likely) and ten class III IgG4 autoimmune diseases, of which five are class IIIa, with insufficient data and five class IIIb, which support pathogenic entities other than IgG4. The pathogenicity of IgG4 in IgG4 autoimmune diseases is associated with blocking of enzymatic activity or protein-protein interaction of their target antigen

Background and Aims

H.R. is 30 years old egyptian woman.

Methods

In Egypt, in 2013, her first son born at 30 weeks of gestation and died after 17 days for “heart disease” (no clinical information provided). In 2016, a daughter born at 34th week: after 9 days the little girl was transferred at Papa Giovanni XXIII hospital’s ICU due to severe respiratory failure with pancarditis and dilated cardiomyopathy. Only high titre AMA-M2 of maternal origin was found without liver alterations for both mother and daughter. The newborn girl, treated with high dose prednisone, recovered completely. In 2018 H.R. started a new pregnancy and beyond AMA-M2, she was found positive for anti Sp-100 antibodies but she showed no signs of cholangitis. At the end of that pregnancy (32 weeks) a low weight newborn girl was born: after two days the little girl showed premature ventricular contractions and repolarisation abnormalities; she was transfer at ICU for cardiac monitoring and treated also with low dose prednisone because, even in this case, she was positive for AMA-M2 and Sp-100 antibodies. She recovered completely after 15 days and showed no problems during the follow up: AMA-M2 antibodies became negative after 7 months.

Results

This case report suggests that AMA could have a role in the pathogenesis of cardiac abnormalities showed by the three siblings.

Conclusions

In literature association between AMA and autoimmune cardiomyopathy is described but only in adult patients: probably because AMA test is not performed in newborn with cardiomyopathy leading to an underestimation of AMA-associated cardiomyopathy cases.

Background and Aims

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a heterogeneous clinical manifestation, posing a major challenge for diagnosis, prognosis and intervention. Autoantibodies against fetal brain antigens have been described in the blood of mothers of children with ASD (m-ASD). These autoantibodies can be transferred from the mother to the fetus by transplacental transport and could impact neurodevelopment by binding to fetal brain proteins. In this study, we aim to identify novel maternal autoantibodies that could be used as biomarkers to assist in ASD diagnosis.

Methods

Methods: A cDNA phage display library expressing human fetal brain antigens was constructed and screened for antibody reactivity in m-ASD plasma. Using enzyme-linked immunosorbent assays (ELISA), presence of antibodies to the identified antigens was tested in 152 m-ASD plasma samples from the Simons Simplex Collection, and in 90 samples from mothers with typically developing children (m-TD) collected at Hasselt University.

Results

Results: Screening and validation of antibody reactivity against antigenic targets resulted in the identification of 10 novel maternal autoantibodies. Antibody reactivity against at least one of these 10 antigens was found in 70% of m-ASD samples, compared to 52% in m-TD samples (p=0.0057). Four antigenic targets showed a specificity higher than 95%, and combined reactivity against them was found in 28% of m-ASD samples compared to 10% in m-TD samples (p=0.0007).

Conclusions

Conclusion: We identified 10 novel maternal autoantibodies which could provide novel targets to study ASD etiology. Additionally, 4 of these autoantibodies, could provide a novel tool for objective diagnosis of a subset of ASD patients.

Background and Aims

IgG-autoantibodies against the high affinity IgE-receptor, FceRIα, are thought to be key features of type IIb autoimmune chronic spontaneous urticaria (CSU). However, it is not known, if in CSU also IgM or IgA autoantibodies against FceRIα exist. The aim was to develop an ELISA to assess serum levels of IgG, IgM and IgA autoantibodies against FceRIα, and to investigate their link to clinical features of CSU.

Methods

We analyzed serum samples of 35 patients with CSU (25 ASST-positive) and 52 healthy controls using a competitive ELISA for determination of IgG, IgM and IgA autoantibodies to FceRIα.

Results

One in four CSU patients (24%) exhibited elevated serum levels of IgG-anti-FceRIα. More than half of the CSU patients had IgM (60%) and IgA (57%) vs 5% each in healthy controls. ASST-positive patients showed most frequent elevated levels of IgM class autoantibodies (72% in ASST pos vs. 30% in ASST neg; P = 0.022). No association was seen with IgG or IgA autoantibodies. Also, elevated levels of IgM-anti-FceRIα, but not of IgG or IgA against FceRIα, were linked to low blood basophil (r = 0.414, P = 0.021) and eosinophil (r = 0.623, P < 0.001) counts, features of high disease activity in CSU.

Conclusions

Our novel assay can detect IgG, IgM and IgA autoantibodies against FceRIα. Increased serum levels of IgM-anti-FceRIα are very common in patients with CSU and showed a link to features of autoimmune CSU. The role and relevance of autoantibodies to FceRIα in CSU should be further characterized in future studies.

Background and Aims

Plastic surgery procedures have been rising in the last few years. The morbi-mortality due to illegal use of biopolymers is a public health problem. One of the clinical consequences, Iatrogenic Alogenosis (IA), may be a precursor of ASIA syndrome.

The objective of this article is to present a case-series study of patients who developed ASIA syndrome following gluteal injection with biopolymers and emphasize the importance of environment factors and toxic exposure in triggering autoimmune responses. A surgical technique used on some of the patients in the study is described.

Methods

A group of thirteen patients, diagnosed with IA, who developed ASIA syndrome confirmed by approved criteria was followed (May 2016-May 2018). The “Butterfly Wings Technique,” a new surgical procedure for patients who have middle to severe compromise, was used on five of them.

A narrative literature review was done to look for subjects with ASIA syndrome and gluteal biopolymer infiltration.

Results

All the patients in the present case-series with IA developed ASIA syndrome. Most of them (9 patients) had a background of environmental factors and familial autoimmunity. Five of the patients were surgically treated and saw a clinical improvement after the extraction of the biopolymer with the proposed technique.

The narrative literature review identified 7 articles related to the disease through the database search.

Conclusions

We suggest that IA should be considered a precursor to ASIA syndrome. New research projects will be needed in the future to evaluate the factors that determine when ASIA syndrome is triggered in a patient with IA.

Background and Aims

Vitiligo, an acquired, multifactorial, autoimmune disorder is classified for therapeutic purposes as progressive and non-progressive. The first priority for the treatment of vitiligo should be to control the disease process, and then taking measures to re-pigment.

Methods

We had three different studies in patients with progressive vitiligo

Results

In progressive disease, there is continuous assault on melanocytes and modalities which do not arrest this process may not work. Corticosteroids suppress autoantibody formation and induces apoptosis of cytotoxic T cells. It helps not only in halting progression of the disease, but also induces re-pigmentation as normal melanocytes from the periphery of the lesions or perifollicular areas take over.

To achieve long-term safety of systemic corticosteroids, we used oral mini-pulse therapy (OMP) in 1993 and since then, most studies indicate that OMP halts disease progression in rapidly spreading vitiligo and induces variable re-pigmentation. To address the need for another immunosuppressant, we compared the efficacy and safety of betamethasone OMP vs oral azathioprine in arresting the disease progression and inducing re-pigmentation. In the OMP group arrest of progression was achieved earlier at 2 and 4 months compared to azathioprine at 6 months. Re-pigmentation was also better in OMP group.

Immunomodulatory effect of NB-UVB is by increasing regulatory T-lymphocytes and inhibiting the number of CD8+ T-lymphocytes. In our study, 19 out of 24 progressive vitiligo patients had halting of disease activity after 6 months of NB-UVB.

Conclusions

To conclude, oral corticosteroid as OMP, azathioprine and NB-UVB in various permutation and combination can be useful in progressive vitiligo.

Background and Aims

Autonomic dysfunction, at least in subsets of patients could develop due to imbalance of functional autoantibodies against autonomic nervous system autoantigens. We have recently diagnosed women with silicone breast implants (SBIs) suffering from various subjective clinical manifestation, among them: paresthesia, hearing abnormalities, increased sweating, heat sensation, cognitive impairment, sleep disturbance, palpitations etc. We hypothesized that dysregulation of the autonomic nervous system in these women may explain, at least in part, some of their enigmatic manifestations.

Methods

A potential direct pathogenic effect of patient-derived autoantibodies will be examined by passive transfer of patients-derived autoantibodies into naïve animals (Localintracerebroventicular (ICV) or intravenous (IV) injections), following evaluation of behavioral and autonomic related manifestations: anxiety level, pain, body temperature and muscle strength.

Results

Preliminary results at our lab, show for the first time the appearance of various circulating autoantibodies against adrenergic and muscarinic acetylcholine receptors in women with SBIs. Furthermore, we show for the first time the appearance of small fiber neuropathy (SFN) in these women. In the current study, we aim to explore the potential pathogenic effect of circulating anti-autonomic receptor autoantibodies from women with SBIs as compared to sex and aged matched control groups (healthy and fibromyalgia).

Conclusions

We believe that examination of anti-autonomic antibodies effect in laboratory animals could help to reveal biomarkers for dysautonomia in genetically susceptible women with SBIs.

The work is supported by a grant from the Government of the Russian Federation (contract 14.W03.31.0009 of 13.02.2017) for state support of scientific research conducted under the supervision of leading scientists.