Welcome to the 13th International Congress on Autoimmunity interactive program
AUTOIMMUNITY AND FIBROMYALGIA SYNDROME: ANY CORRELATION? (ID 930)
NOVEL ANTIBODY BIOMARKERS FOR DIAGNOSIS OF AXIAL SPONDYLOARTHRITIS (ID 934)
IS045 - PULMONARY PEMPHIGOID- NEW DISEASE ENTITY (ID 936)
Abstract
Abstract Body
ABSTRACT
Background: Mucous membrane pemphigoid is an autoimmune subepidermal/submucosal disease, characterized by blisters, erosions. Its unique feature is that as the blister heal they cause irreversible scarring, which may be fatal or significantly affect the quality of life. While upper airway involvement is well studied, lower airway involvement has not been characterized. This review describes the clinical presentation, diagnosis, and treatment of pulmonary pemphigoid, present in the literature.
OBSERVATIONS: We searched Pubmed, Embase, Medline, and Google Scholar databases from inception to October 2021. 11 original case reports describing mucous membrane pemphigoid patients with biopsy and immunopathology proven tracheal and bronchial involvement were included in this review. Among 11 patients with mucous membrane pemphigoid of the lower airways, 80% were under 40 years of age. All had severe widespread mucous membrane pemphigoid involving three or five mucosal tissues. Involvement of oral cavity occurred in 100% of cases. Ocular and cutaneous involvements were seen in 82% of patients. Pulmonary involvement occurred at 24 mo (range 2-372) after the onset of mucous membrane pemphigoid. Bronchoscopy revealed acute inflammation during active disease and scarring of the trachea and bronchi in the later stage. Systemic infections occurred in 45% of the patients while the pulmonary infection occurred in 36%. Mortality due to respiratory failure at the median age of 20 years (range 18-76), occurred in 45% of the patients.
CONCLUSIONS: The young age, similarity in clinical profile, clinical course, response to systemic therapy, and high mortality warrant early recognition of pulmonary pemphigoid. These patients differ from other mucous membranous patients. Thus far it is a less recognized entity. The diagnosis could have been possibly missed in many cases. The cause of death appears to be disease related. Early diagnosis with appropriate management could produce better clinical outcomes and prevent mortality.
O116 - ANTI-CD45RC ANTIBODY IMMUNOTHERAPY PREVENTS AND TREATS EXPERIMENTAL AUTOIMMUNE POLYENDOCRINOPATHY CANDIDIASIS ECTODERMAL DYSTROPHY SYNDROME (ID 514)
Abstract
Background and Aims
Targeted monoclonal antibody (mAb) therapies show great promise for the treatment of transplant rejection and autoimmune diseases by inducing more specific immunomodulatory effects than broadly immunosuppressive drugs routinely used. We recently described the therapeutic advantage of targeting CD45RC, expressed at high levels by conventional T cells (Tconv, CD45RChigh), their precursors and terminally differentiated T (TEMRA) cells, but not by regulatory T cells (Tregs, CD45RClow/-). We demonstrated efficacy of anti-CD45RC mAb treatment in transplantation but its potential has not been examined in autoimmune diseases. APECED is a rare genetic syndrome caused by loss-of-function mutations of the key central tolerance mediator, autoimmune regulator (AIRE) leading to abnormal auto-reactive T cell responses and autoantibodies production.
Methods
3 weeks old Aire-/- rat were injected by intraperitoneal twice a week with either anti-CD45RC mAbs or isotype control mAbs at 1,5mg/kg. After 4 months of treatment animals were sacrificed for organs harvesting.
Results
Herein, we showed that, in a rat model of APECED syndrome, anti-CD45RC mAb was effective both as prevention and treatment of autoimmune manifestations and inhibited autoantibody development. Anti-CD45RC mAb intervention depleted CD45RChigh T cells, inhibited CD45RChigh B cells, and restored the Treg/Tconv ratio and the altered Tregs transcriptomic profile. In APECED patients, CD45RC was significantly increased in peripheral blood T cells and lesioned organs from APECED patients were infiltrated by CD45RChigh cells.
Conclusions
Our observations highlight the potential role for CD45RChigh cells in the pathogenesis of experimental and human APECED syndrome and the potential of anti-CD45RC antibody treatment.
O117 - A ROLE FOR AUTOIMMUNITY IN SARCOID UVEITIS? (ID 560)
Abstract
Background and Aims
Uveitis is a common disease manifestation in sarcoidosis. It is currently unclear whether an autoimmune response is involved in sarcoid uveitis. Here, we explored a potential role for an autoimmune response in sarcoid uveitis.
Methods
In total 91 sarcoidosis patients of whom 46 with uveitis and 45 without uveitis were included. Presence of serum anti-retinal antibodies (ARA) was determined by indirect immunofluorescent staining. Low-resolution HLA-class II typing was performed and T-cell receptor (TCR) and B-cell receptor (BCR) repertoire analysis was performed by next generation sequencing. TCR/BCR clonotypes were clustered based on complementary determining region 3 (CDR3) amino acid sequences. 384 inflammation related serum protein levels were measured.
Results
Serum ARA were detected in significantly more sarcoid uveitis patients than sarcoidosis patients without uveitis and healthy controls. No association was observed between sarcoid uveitis and HLA-class II. TCR and BCR repertoire analysis revealed 73 TCR clusters and 11 BCR clusters exclusively present in sarcoid uveitis patients. ARA positivity was associated with significantly higher serum IFN-γ levels and within uveitis patients with lower serum motilin levels.
Conclusions
This study shows for the first time a clear association between serum ARA and sarcoid uveitis. This finding indicates that an anti-retinal autoimmune response occurs frequently in sarcoid uveitis cases. This is further corroborated by the association of sarcoid uveitis with specific TCR/BCR clonotypes. Sarcoid uveitis was also associated with decreased serum motilin levels previously linked to autoimmunity. Moreover, ARA positivity in sarcoid uveitis was associated with increased serum IFN- γ levels, suggesting a stronger Th1 response.
O118 - ANTI-NEURONAL IGG4 AUTOIMMUNE DISEASES AND IGG4-RELATED DISEASES MAY NOT BE PART OF THE SAME SPECTRUM: A COMPARATIVE STUDY (ID 565)
Abstract
Background and Aims
IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features.
Methods
We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD.
Results
A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD.
Conclusions
Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.
O119 - ACHALASIA — AN AUTOIMMUNE INFLAMMATORY DISEASE? (ID 685)
Abstract
Background and Aims
Background: Idiopathic achalasia is an esophageal motor disorder, characterized by loss of enteric neurons leading to absence of peristalsis and impaired relaxation of the lower esophageal sphincter (LES). The physiopathology of achalasia is still unknown, although an autoimmune etiology is suspected.Aim: We aim to determine whether autoantibodies against the autonomic nervous system receptors can explain the enigmatic pathogenesis of achalasia.
Methods
An observational cross-sectional study using an ELISA method designed to identify the level of: 1) Circulating autoantibodies against G protein-coupled receptors of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors). 2) Coexistence autoantibodies including: anti-nuclear antibody (ANA), anti-Ro, anti-La, antibodies to insulin, islet cell autoantibodies (ICA), anti-glutamic acid decarboxylase (anti-GAD), anti-thyroid peroxidase antibody (anti-TPO), anti-thyroid stimulating immunoglobulin (TSI) antibody, anti-gastric parietal cell antibody (GPC), anti-smooth muscle antibody (ASMA), and anti-mitochondrial (AMA). Peripheral blood will be obtained from forty achalasia patients diagnosed by an expert gastroenterologist based on esophageal manometry and upper endoscopy findings. The medical records of each patient will be reviewed. Peripheral blood will also be obtained from forty matched healthy donors (HD) with no diagnosis of achalasia. We will interview HDs in order to discard any history of an autoimmune disease, as well as any symptom suggestive for upper motility disorder.Results
Pending.Conclusions
Pending.O120 - AUTOIMMUNITY AND POTENTIAL ANTIGENIC TARGETS IN SCLERITIS (ID 293)
Abstract
Background and Aims
Scleritis is a potentially blinding ocular disorder, with largely unknown pathogenesis and unpredictable course. We hypothesize an autoimmune origin of scleritis, and analyzed the prevalence and clinical relevance of well-known systemic autoantibodies, possible scleral-associated autoantibodies, and potential antigenic targets in non-infectious scleritis.
Methods
We performed a retrospective analysis on the presence of ANA, ANCA, rheumatoid factor, and anti-citrullinated protein antibodies (ACPA) in patients with non-infectious scleritis (N=81). We also prospectively evaluated sera of 20 patients on the presence of potential scleral-associated auto-reactivity using indirect immunofluorescence with primate ocular tissue sections, and Western Blot with human scleral tissue. Further, we collected scleral tissues affected by scleritis (N=3), as well as control sclera (N=5) for a mass spectrometry based proteomic analysis.
Results
In 81 patients with scleritis, positive ANA was found in 30%, ANCA was positive in 19%, mostly anti-PR3 specific, and the presence of rheumatoid factor was shown in 17%. ACPA in the context of rheumatoid arthritis were found in 9% of scleritis patients, and were significantly associated with the development of scleral necrosis (P=0.01). 25% of patients showed scleral auto-reactivity on indirect immunofluorescence without confirmation on Western blot. Mass spectrometry identified filaggrin-2 to be significantly upregulated in scleral tissue affected by scleritis (P=0.0001).
Conclusions
No evidence for scleral-associated autoantibodies was found so far in non-infectious scleritis patients. However, the presence of ACPA was significantly associated with the development of scleral necrosis as complication of scleritis. Further research is ongoing to investigate the role of fillagrin-2 as potential antigenic target in scleritis.
O121 - AUTOIMMUNITY AND PSYCHOSIS: MORE THAN A COINCIDENCE (ID 1031)
Abstract
Background and Aims
While autoimmunity spares no body organ or system, it is nevertheless becoming more widely recognized as an etiologic factor in psychoses. For instance, antibody-mediated encephalitides are a group of diseases associated with neuropsychiatric symptoms presenting with antibodies against various neuronal cell components such as cell-surface proteins, ion channels, and receptors. Additionally, autoimmune encephalitides fall into a category separate from other autoimmune diseases that may cause neuropsychiatric symptoms, namely systemic lupus erythematosus.
Methods
With advancing studies, it appeared that not all cases of autoimmune encephalitides result in psychosis, thus paving the path for a new sub-category: autoimmune psychosis.
Results
While genetic predisposition is the greatest hit, there are two main potential triggers: viruses and tumors. Herpes simplex encephalitis can trigger antibodies against N-methyl-D-aspartate receptor (NMDAR). However, anti-NMDAR autoimmune encephalitis makes up most but not all causes of autoimmune psychosis. Furthermore, antibodies against diversely different bodily tissues also act out different roles in the many present psychotic disorders such as Hashimoto’s encephalopathy.
Conclusions
Between two-hit hypotheses, comorbidities, and the COVID-19 pandemic, the medical literature yields extensive riches that need to be organized and well-acknowledged.We aimed to review the medical literature on the relationship and associations between autoimmunity and psychosis in terms of triggers, pathophysiology, and autoimmune aspects.