Spectrum Of Autoimmune Diseases Research Articles

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Prevalence and Spectrum of Autoimmune Diseases Among Patients with Telomere Biology Disorder

Introduction Telomeres are the protective ends of linear chromosomes that prevent DNA degradation with each replication. Premature attrition or dysfunction of telomeres due to an inherited defect in a telomere maintenance gene results in a spectrum of phenotypes collectively known as telomere biology disorders (TBD). To date, 18 genes have been implicated in TBD. Disease phenotypes are variable including bone marrow failure, immunodeficiency, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), idiopathic pulmonary fibrosis (IPF), liver cirrhosis, nail dystrophy, and premature graying of hair. Short telomeres have been observed in patients with autoimmune disorders (AID) and have been shown to increase the risk of AID. Furthermore, TBD have been associated with T cell dysfunction and exhaustion, mechanisms which may predispose to autoimmune phenotypes. Given the potential relationship between short telomeres and immune dysregulation, we hypothesize that the prevalence of AID may be increased in patients with a diagnosis of TBD. The aim of this study is to describe the prevalence and spectrum of AID in a cohort of patients with TBD. Methods Health record data were reviewed for 34 adult patients with confirmed TBD treated at the University of Wisconsin-Madison. A TBD diagnosis was established for patients who had a compatible clinical history plus either critically short lymphocyte telomere lengths (<1 st percentile for age as measured by FlowFISH) or one or more pathogenic/likely pathogenic variant(s) in a gene known to cause TBD. Demographics, rheumatologic history, serologies, and family history were collected. AID were included if diagnoses were made by a rheumatologist or other appropriate specialist with clinical features, physical exam findings, and/or serologies meeting diagnostic criteria per subspecialty guidelines. Results Eight of 34 patients (23.5%) with TBD had a concomitant diagnosis of a primary autoimmune condition. Specific AID included inflammatory bowel disease, Graves' disease, Hashimoto's thyroiditis, rheumatoid arthritis, scleroderma, and Sjogren's syndrome (Table 1). Two patients had autoimmune cytopenias, including steroid-responsive immune thrombocytopenic purpura and pure red cell aplasia (PRCA). Patient 8 was diagnosed with PRCA mixed with spur cell anemia prior to transplant, and bone marrow biopsy showed pure erythroid hypoplasia without evidence of malignancy. He responded to treatment with steroids and immunosuppression. Of the eight patients with a primary autoimmune condition, two had pathogenic/like pathogenic variants, two had rare variants of uncertain significance, and four had no detectable variants in a telomere associated gene. Twenty-three patients (67.6%) had a first- or second-degree relative with an autoimmune disorder. Conclusions An AID, as defined by strict diagnostic criteria per subspecialty guidelines, was present in 23.5% of patients with TBD defined by conservative diagnostic criteria. The spectrum of AID was diverse, including two patients with autoimmune hematologic disorders, and the majority had a family history of various AID. Thus, TBD may be associated with an increased prevalence of AID, though confirmation in a larger cohort of genetically defined TBD patients is needed. In the absence of a causative genetic lesion, diagnosis of a TBD based on critically short telomeres in those with multisystem autoimmune disorders with features that overlap TBD phenotypes can be challenging. Screening for AID as part of routine TBD comprehensive assessments as well as offering germline genetic testing for individuals with primary autoimmune disease with a compatible TBD phenotypes and studies to determine the mechanistic relationship between telomere length and autoimmunity are warranted.

IFIH1 and DDX58 gene variants in pediatric rheumatic diseases.

The IFIH1 gene codes the MDA5 protein and the DDX58 gene codes the RIG-I receptor. Both proteins are parts of the interferon (IFN) I signaling pathway and are responsible for antiviral defense and innate immune response. IFIH1 and DDX58 polymorphisms are associated with a spectrum of autoimmune diseases. Rare gain-of-function IFIH1 mutations have been found in Singleton-Merten and Aicardi-Goutières syndrome, while DDX58 mutation can cause atypical Singleton-Merten syndrome. To characterize children with pediatric rheumatic diseases (PRD) carrying DDX58 or IFIH1 variants. Clinical exome sequencing was performed on 92 children with different PRD. IFIH1 and DDX58 variants have been detected in 14 children. IFN-I score has been analyzed and the clinical characteristics of patients have been studied. A total of seven patients with systemic lupus erythematosus (SLE) (n = 2), myelodysplastic syndrome with SLE features at the onset of the disease (n = 1), mixed connective tissue disease (MCTD) (n = 1), undifferentiated systemic autoinflammatory disease (uSAID) (n = 3) have 5 different variants of the DDX58 gene. A common non-pathogenic variant p.D580E has been found in five children. A rare variant of uncertain significance (VUS) p.N354S was found in one patient with uSAID, a rare likely non-pathogenic variant p.E37K in one patient with uSAID, and a rare likely pathogenic variant p.Cys864fs in a patient with SLE. Elevated IFN-I score was detected in 6 of 7 patients with DDX58 variants. Seven patients had six different IFIH1 variants. They were presented with uSAID (n = 2), juvenile dermatomyositis (JDM) (n = 1), SLE-like disease (n = 1), Periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome (n = 1), and systemic onset juvenile idiopathic arthritis (n = 1). Three patients have VUS p.E627X, one patient has benign variant p.I923V. Rare VUS p.R595H was detected in the JDM patient. Another rare VUS p.L679Ifs*2 and previously not reported variant p.V599Ffs*5 were detected in the patient with uSAID. One patient with uSAID has rare VUS p.T520A. All patients had elevated IFN-I scores. Rare compound-heterozygous IFIH1 variant (p.L679Ifs*2 and p.V599Ffs*5), heterozygous IFIH1 variant (p.T520A) and heterozygous DDX58 variant (p.Cys864fs) are probably disease causative for uSAID and SLE. The majority of patients with different DDX58 and IFI1 variants had hyperactivation of the IFN I signaling pathway.

Extrathymic expression of Aire controls the induction of effective TH17 cell-mediated immune response to Candida albicans.

Patients with loss of function in the gene encoding the master regulator of central tolerance AIRE suffer from a devastating disorder called autoimmune polyendocrine syndrome type 1 (APS-1), characterized by a spectrum of autoimmune diseases and severe mucocutaneous candidiasis. Although the key mechanisms underlying the development of autoimmunity in patients with APS-1 are well established, the underlying cause of the increased susceptibility to Candida albicans infection remains less understood. Here, we show that Aire+MHCII+ type 3 innate lymphoid cells (ILC3s) could sense, internalize and present C. albicans and had a critical role in the induction of Candida-specific T helper 17 (TH17) cell clones. Extrathymic Rorc-Cre-mediated deletion of Aire resulted in impaired generation of Candida-specific TH17 cells and subsequent overgrowth of C. albicans in the mucosal tissues. Collectively, our observations identify a previously unrecognized regulatory mechanism for effective defense responses against fungal infections.

Autoimmune Hashimoto thyroiditis with concomitant autoimmune hepatitis

So far, the literature data have presented a combination of several autoimmune triggered disease in patients, but the research is scarce and very limited. In this context we present a rare case of autoimmune thyroiditis with a concomitant autoimmune hepatitis. Hashimoto thyroiditis is an autoimmune disorder in which immune cells lead to impairment, destruction of the thyroid hormone producing cells and tissue fibrosis with consecutive primary hypothyroidism. Autoimmune hepatitis is a chronic liver disease with unknown etiology, which is assumed to be T cell mediated condition where immune cells produce autoantibodies responsible for inflammation, destruction and fibrosis of the hepatic parenchyma. In this case report, we discuss the possible correlation in the spectrum of autoimmune diseases concerning Hashimoto thyroiditis and autoimmune hepatitis.

The influence of reproductive hormones on systemic lupus erythematosus

Humans are afflicted by a wide spectrum of autoimmune disorders, ranging from those affecting just one or a few organs to those associated with more systemic effects. In most instances, the etiology of such disorders remains unknown; a consequence of this lack of knowledge is a lack of specific treatment options. Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disorder; pathology is believed to be antibody-mediated, and multiple organs are targeted. Periods of disease “flares” are often followed by long periods of remission. The fact that SLE is more commonly observed in females, and also that it more particularly manifests in females in the reproductive age group, has quite naturally drawn attention to the potential roles that hormones play in disease onset and progression. This review attempts to shed light on the influences that key hormones might have on disease indicators and pathology. Databases (Google Scholar, PubMed) were searched for the following keywords (sometimes in certain combinations), in conjunction with the term “lupus” or “SLE”: autoantibodies, recurrent abortion, polycystic ovarian syndrome (PCOS), preeclampsia, pre-term delivery, estrogens, progesterone, androgens, prolactin, leptin, human chorionic gonadotropin (hCG). Cited publications included both research articles and reviews.

Type I interferon detection in autoimmune diseases: challenges and clinical applications

ABSTRACT Introduction Accumulating data highlights that the dysregulation of type I interferon (IFN) pathways plays a central role in the pathogenesis of several systemic and organ-specific autoimmune diseases. Advances in understanding the role of type I IFNs in these disorders can lead to targeted drug development as well as establishing potential disease biomarkers. Areas covered Here, we summarize current knowledge regarding the role of type I IFNs in the major systemic, as well as organ-specific, autoimmune disorders, including prominent inflammatory CNS disorders like multiple sclerosis. Expert opinion Type I IFN involvement and its clinical associations in a wide spectrum of autoimmune diseases represents a promising area for research aiming to unveil common pathogenetic pathways in systemic and organ-specific autoimmunity.

Rituximab induced acute thrombocytopenia in a patient with systemic lupus erythematosus: a case report

BackgroundRituximab is a novel chimeric monoclonal antibody that has established itself as a potent therapeutic option for autoimmune medical conditions, including systemic lupus erythematosus, owing to its mechanism of action targeting CD20 cells. Rituximab is also known to cause a spectrum of side effects including hematological abnormalities. Acute isolated thrombocytopenia following rituximab is an uncommon occurrence and, when seen, occurs in the presence of underlying hematological malignancies. Its occurrence in autoimmune diseases is rare. Despite this, acute isolated thrombocytopenia in the backdrop of systemic lupus erythematosus is undocumented.Case presentationA young 36-year-old South Asian female with systemic lupus erythematosus with class IV lupus nephritis poorly responding to standard therapy was initiated on rituximab. Ten days later, she presented with mucocutaneous bleeding and ecchymotic skin lesions. Isolated severe thrombocytopenia was noted with a platelet count of 5 × 109/L (150–450). Anticipating life-threatening bleeding, she was given intravenous immunoglobulin, methyl prednisolone, and platelet transfusion considering a spectrum of initial differential diagnosis. Rituximab was also withheld. Though extensively investigated, most investigations were negative. A platelet destructive process was suspected as bone marrow biopsy showed adequate megakaryocytes. Weighing the risk versus benefit, following recovery, she was reinitiated on rituximab. Within 4 days, she presented again with similar symptoms and severe isolated thrombocytopenia was noted. Rituximab-induced acute thrombocytopenia was considered the working clinical diagnosis.Case discussion and conclusionRituximab can cause a spectrum of hematological abnormalities, including isolated acute thrombocytopenia. Its occurrence in autoimmune conditions is rare, and its manifestation in systemic lupus erythematosus is undocumented. Its exact etiology is still disputed. Usually considered benign, the platelet numbers tend to show improvement with cessation of therapy. However, in the presence of mucocutaneous bleeding in our patient, we took an aggressive approach to management. Though evidence for corrective therapy is anecdotal, it could be justified on the basis of averting potential catastrophic hemorrhagic manifestations. The spectrum of autoimmune disease that potentially predisposes rituximab to cause thrombocytopenia should be extended to include systemic lupus erythematosus.

Glaucoma is an autoimmune disease.

Glaucoma is characterized by retinal ganglion cell (RGC) neurodegeneration. Elevated intraocular pressure (IOP) is a major risk factor however, mechanisms independent of IOP play a role in RGC pathology. Both antibodies and CD4 T-cells as well as microbiota take part in the pathogenesis of both glaucoma and rheumatoid arteritis (RA).Heat shock proteins (HSPs) which originate in bacteria cross-react with RCG epitopes and were involved in rat model of retinal injury. Enhanced expression of HSPs in the retina was associated with glaucoma-like neuropathology and previous studies have also suggested a pathogenic role for HSPs in RA. In view of these data we suggest that glaucoma should be included in the spectrum of autoimmune diseases and that proven medications for RA should be adopted as an innovative IOP -independent therapeutic strategy for glaucoma.

Acute tubulointerstitial nephritis and IgM deposits on glomerular capillary walls after immunotherapy with nivolumab for metastatic renal cell carcinoma

Nivolumab is an anti-programmed cell death-1 antibody that is utilized as an immune checkpoint inhibitor for several malignancies. However, this agent is associated with immune-related adverse events (irAEs), mainly in the spectrum of autoimmune disease including interstitial pneumonia, colitis, type 1 diabetes, and renal impairment. We herein present the case of a 59-year-old man with renal cell carcinoma who developed worsening renal function approximately 4 months after initiation of nivolumab. Urinalysis showed proteinuria and microscopic hematuria along with increase levels of N-acetyl-β-d-glucosaminidase. Renal biopsy revealed acute tubulointerstitial nephritis and thickening of the glomerular basement membranes. Immunofluorescence showed granular IgM deposits in capillary loops. We initiated high-dose prednisolone therapy with nivolumab, which improved renal function and achieved complete remission of proteinuria. Although renal irAEs are considered to be rare and glomerulonephropathy is not typical presentation, physicians need the close monitoring of renal function and urinalysis in patients under immunotherapy with this agents. In addition, our case provides a possible link between nivolumab and immune-mediated glomerulonephropathy.

Identification and structure–function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22

Protein-tyrosine phosphatase nonreceptor type 22 (PTPN22) is a lymphoid-specific tyrosine phosphatase (LYP), and mutations in the PTPN22 gene are highly correlated with a spectrum of autoimmune diseases. However, compounds and mechanisms that specifically inhibit LYP enzymes to address therapeutic needs to manage these diseases remain to be discovered. Here, we conducted a similarity search of a commercial database for PTPN22 inhibitors and identified several LYP inhibitor scaffolds, which helped identify one highly active inhibitor, NC1. Using noncompetitive inhibition curve and phosphatase assays, we determined NC1's inhibition mode toward PTPN22 and its selectivity toward a panel of phosphatases. We found that NC1 is a noncompetitive LYP inhibitor and observed that it exhibits selectivity against other protein phosphatases and effectively inhibits LYP activity in lymphoid T cells and modulates T-cell receptor signaling. Results from site-directed mutagenesis, fragment-centric topographic mapping, and molecular dynamics simulation experiments suggested that NC1, unlike other known LYP inhibitors, concurrently binds to a "WPD" pocket and a second pocket surrounded by an LYP-specific insert, which contributes to its selectivity against other phosphatases. Moreover, using a newly developed method to incorporate the unnatural amino acid 2-fluorine-tyrosine and 19F NMR spectroscopy, we provide direct evidence that NC1 allosterically regulates LYP activity by restricting WPD-loop movement. In conclusion, our approach has identified a new allosteric binding site in LYP useful for selective LYP inhibitor development; we propose that the 19F NMR probe developed here may also be useful for characterizing allosteric inhibitors of other tyrosine phosphatases.

Autoimmune disease-associated non-Hodgkin's lymphoma-a large retrospective study from China.

The incidence and clinical implications of autoimmune diseases (ADs) in patients with non-Hodgkin's lymphoma(NHL) remain unclear. The aim of this study was to examine the prevalence of ADs in NHL and define the clinical characteristics and prognosis of AD-associated NHL patients. Patients diagnosed with NHL in our institute between 1995 and 2017 were retrospectively reviewed to assess the incidence of ADs. Of 4880 patients with NHL, 140 (2.9%) presented with autoimmunity, with a total of 24 ADs. The most common AD was Sjögren syndrome, followed by autoimmune cytopenia, psoriasis, rheumatoid arthritis, etc. Psoriasis and rheumatoid arthritis were significantly associated with pre-existing ADs, whereas autoimmune cytopenia was significantly associated with secondary AD. Sjögren syndrome was significantly associated with B-cell lymphoma, and systemic vasculitis was significantly associated with T-cell lymphoma. Patients with AD-associated NHL had a high frequency of extranodal involvement(87%), with significant associations between specific extranodal sites of lymphoma and subtypes of ADs. Among patients with available data on pre-treatment peripheral blood Epstein-Barr virus (EBV) DNA(n= 68), elevated EBV-DNA load was observed in a variety of NHL subtypes, including 20% of marginal zone lymphoma and 14.3% of follicular lymphoma patients. In a matched-pair analysis, survival did not differ significantly between NHL patients with and without ADs. However, for NHL patients with pre-existing ADs, a prior history of systemic corticosteroids therapy was significantly associated with worse survival (HR = 7.33, P= 0.006). Taken together, our data suggest that a broad spectrum of ADs is associated with NHL, and AD-associated NHL has distinct features with regard to clinical manifestations and prognosis.

Risk Factors Associated with the Occurrence of Autoimmune Diseases in Adult Coeliac Patients.

Objectives Autoimmune diseases (AD) may be associated with coeliac disease (CD), but specific risk factors have been poorly investigated. The aim of this study was to assess the spectrum of AD and its specific risk factors associated in a series of adult coeliac patients. Materials and Methods We performed a single-center case-control study including adult newly diagnosed CD patients. To evaluate the risk factors of the association between AD and CD, 341 coeliac patients included were categorized on the basis of AD presence: 91 cases with at least one AD and 250 controls without AD were compared for clinical, serological, and histological features. Eighty-seven cases were age-gender-matched with 87 controls. Results Among 341 CD patients, 26.6% of CD patients had at least one AD. Endocrine and dermatological diseases were the most prevalent AD encountered: autoimmune thyroiditis was present in 48.4% of cases, psoriasis in 17.6%, and type I diabetes and dermatitis herpetiformis in 11%, respectively. At logistic regression, factors associated with AD were a positive 1st-degree family history of AD (OR 3.7, 95% CI 1.93–7), a body mass index ≥ 25 kg/m2 at CD diagnosis (OR 2.95%, CI 1.1–3.8), and long standing presentation signs/symptoms before CD diagnosis (>10 years) (OR 2.1, 95% CI 1.1–3.7). Analysis on age-gender-matched patients confirmed these results. Conclusions CD patients with family history of AD, overweight at CD diagnosis, and a delay of CD diagnosis had an increased risk of having another AD. The benefit of CD screening in these specific subsets of patients with AD awaits further investigation.

Polyautoimmunity in Patients with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency

ABSTRACTBackground: Polyautoimmunity is defined as the presence of more than one autoimmune disorder in a single patient. Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) deficiency is one of the monogenic causes of polyautoimmunity. The aim of this study was to report the characteristics of polyautoimmunity in patients with LRBA deficiency.Methods: A total of 14 LRBA deficiency patients with confirmed autoimmunity were enrolled in this study. For those patients with polyautoimmunity, demographic information, clinical records, laboratory, and molecular data were collected. We also compared our results with the currently reported patients with LRBA deficiency associated with polyautoimmunity.Results: In 64.2% (9 out of 14) of patients, autoimmunity presented as polyautoimmunity. In these patients, autoimmune cytopenias were the most frequent complication, observed in seven patients. Three patients presented with four different types of autoimmune conditions. The review of the literature showed that 41 of 72 reported LRBA deficient patients (74.5%) had also polyautoimmunity, with a wide spectrum of autoimmune diseases described. Hematopoietic stem cell transplantation is increasingly used as the treatment for patients with severe polyautoimmunity associated to LRBA deficiency.Conclusions: Mutation in LRBA gene is one of the causes of monogenic polyautoimmunity. Awareness of this association is important in order to make an early diagnosis and prompt treatment.

IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders.

Immunoglobulin 4 (IgG4) is one of four human IgG subclasses and has several unique functional characteristics. It exhibits low affinity for complement and for most Fc receptors. It furthermore has generally high affinity for its antigen, with binding occurring in a monovalent fashion, as IgG4 can exchange Fab-arms with other IgG4 molecules. Because of these characteristics, IgG4 is believed to block its targets and prevent inflammation, which, depending on the setting, can have a protective or pathogenic effect. One example of IgG4 pathogenicity is muscle-specific kinase (MuSK) myasthenia gravis (MG), in which patients develop IgG4 MuSK autoantibodies, resulting in muscle weakness. As a consequence of the distinct IgG4 characteristics, the pathomechanism of MuSK MG is very different from IgG1-and IgG3-mediated autoimmune diseases, such as acetylcholine receptor MG. In recent years, new autoantibodies in a spectrum of autoimmune diseases have been discovered. Interestingly, some were found to be predominantly IgG4. These IgG4-mediated autoimmune diseases share many pathomechanistic aspects with MuSK MG, suggesting that IgG4-mediated autoimmunity forms a separate niche among the antibody-mediated disorders. In this review, we summarize the group of IgG4-mediated autoimmune diseases, discuss the role of IgG4 in MuSK MG, and highlight interesting future research questions for IgG4-mediated autoimmunity.

The Role of Autoantibodies to the Extracellular Regions of Ionotropic Receptors in the Etiology and Pathogenesis of Autoimmune Diseases

In the last years it was shown that autoantibodies to the extracellular regions of the ionotropic receptors, such as glutamate AMPA- and NMDA-receptors, GABAA-receptors, glycine and nicotinic acetylcholine receptors, induce a wide spectrum of autoimmune diseases, including limbic encephalitis, Rasmussen's encephalitis, systemic lupus erythematosus, myasthenia gravis, encephalomyelitis, and stiff-man syndrome. In the review the literature data concerning the autoimmune processes provoking autoantibodies formation to the ionotropic receptors, the epitopes participating in the induction of pathogenic autoantibodies, and the effects of these antibodies on the functions of nervous cells and their role in the development of autoimmune diseases were analyzed and systematized. The possible role of oncology diseases in the generation of autoantibodies to the ionotropic receptors was discussed. Approaches that are currently being developed to inhibit the synthesis of pathogenic autoantibodies and to their neutralization were considered. These approaches may be subsequently used to treat the autoimmune diseases caused by the antibodies to ionotropic receptors.

Macrophage activation syndrome in a Case of dermatomyositis overlapping syndrome with systemic lupus erythematosus: A case report

Introduction Macrophage activation syndrome (MAS) is a rare but aggressive life-threatening auto-immune disease. It is characterized by fever, rash, splenomegaly, blood cytopenia, hypertriglyceridemia, high ferritin levels, liver insufficiency, coagulopathy and neurologic involvement. Persistent activation of inflammatory cells like macrophages, natural killer cells and cytotoxic lymphocytes can lead to a cytokine storm and multi organ damage. MAS is usually triggered by rheumatologic diseases and rarely in the presentation of a new connective disease like systemic lupus erythematosus (SLE). In addition to MAS, the auto-immune conditions of SLE can be associated with different overlapping syndromes notably dermatomyositis. Case description We present a 31-year-old male from a Latin-American background without pre-existent conditions who presented complains of sore throat, joint pain, fever and fatigue. He quickly developed a pancytopenia with increased liver and pancreatic enzymes. In the process of the investigation, he was treated with antibiotics and admitted intubated to the intensive care unit for a severe pneumonia. Result and conclusion We proceeded with a bone marrow biopsy which detected an active MAS. Regarding his muscle weakness, we also revealed an inflammatory myositis on a quadricep muscle biopsy. Further discovery of positive auto-antibodies (ANA and anti-DNA) showed the presence of a LED. We successfully treated his different auto-immune complications with high doses of prednisone, and intravenously immunoglobulins. After 2 months of his admission and 12 days passed in the intensive care unit, the patient returned home with minimal sequelae with a long term immunosuppressive treatment of prednisone, mycophenolate mofetil and hydroxychloroquine. Take-home message The early identification of the cause of MAS is crucial for the accurate management of this disease and preventing further multi organ complications. SLE has remains a complex condition that can present its first manifestations in a broad spectrum of auto-immune diseases.

Chronic Autoimmune Epithelitis in Sjögren's Syndrome and Primary Biliary Cholangitis: A Comprehensive Review.

Within the spectrum of autoimmune diseases, Sjögren’s syndrome and primary biliary cholangitis are exemplary and can be coined as chronic epithelitis based on their frequent coexistence in clinical practice and the highly specific immune-mediated injury of the small bile ducts and the exocrine glands. The pathogenic mechanisms underlying the diseases are similar, with apoptosis being the key element leading to organ-specific immune-mediated injury directed against the small bile ducts and salivary gland epithelia, respectively along with similar epidemiological features, such as female predominance and the age of onset in the fifth decade of life. Indeed, novel insights into the pathogenesis of the diseases have been obtained in recent years, including a better definition of the role of B and T cells, particularly Th17 cells, and the mechanisms of autoantibody-mediated tissue injury, with anti-mitochondrial antibodies and SS-A/SS-B being identified as specific for primary biliary cholangitis and Sjögren’s syndrome, respectively. These findings have opened the possibility to new targeted therapies, but most clinical needs remain unmet, particularly from a therapeutic standpoint where options diverge, with bile acids being the predominant treatment strategy in primary biliary cholangitis and immunomodulators being used to treat Sjögren’s syndrome. Here we provide a comprehensive review of the most recent findings on the pathogenesis, clinical manifestations and therapeutic options for Sjögren’s syndrome and primary biliary cholangitis, respectively, while stressing the common traits between these conditions. Our cumulative hypothesis is that similarities outnumber differences and that this may prove advantageous towards a better management of patients.

MECHANISMS OF IMMUNOLOGICAL TOLERANCE DISRUPTION

Autoimmune diseases belong to disorders with an unclear etiology. The spectrum of autoimmune diseases is wide, the most well known of them are type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Crohn’s disease, vitiligo, and others. The key role in the development of autoimmune reactions is played by disturbances of immunological homeostasis. Despite numerous researches, the exact mechanisms of autoimmunity still remain unclear. The analysis of data provided by the literature on the mechanisms of disorders of immunological tolerance is presented in the review. The most discussed theories of pathological autoimmune processes development are described: the theory of hereditary predisposition, the theory of immunological dysregulation and regulatory T-cell dysfunction, the theory of network regulation, the infectious theory of autoimmune diseases development (molecular mimicry, polyclonal activation of lymphocytes). The theory of hereditary predisposition reflects the critical role of hereditary factors in the development of autoimmunity, in particular, the data on relations of autoimmune disorders to human major histocompatibility complex are provided. In addition, the data indicating that the development of autoimmune processes in an organism can be associated with changes in the content and function of regulatory T-lymphocytes are provided in the work. These cells are directly involved in the mechanisms of cellular immune responses in autoimmune diseases and may explain the disorders of immunological tolerance, subsequently leading to the development and progression of immunopathology. The idea of idiotype-anti-idiotype interactions, which can serve as a mechanism ensuring normal autoimmune reactions or lead to the activation of autoreactive clones, is revealed in the description of network regulation theory. The infectious theory of development of autoimmune pathologies presented in the review is based on the results of numerous researches and suggests that the viruses can provoke failures of immunity and lead to autoimmunity.

Which Skin Lupus Criteria are of More Value in Determining the Disease: A Greater View with the Help of Direct Immune Fluorescent (DIF)

Background: Lupus erythematous (LE) describes a spectrum of auto immune disorders, involving whole body (systemic LE) in one end and cutaneous limited LE on the other side. Cutaneous LE mainly diagnosed via clinical manifestations as well as histopathologic examination. According to different pathologic specifications, the aim of present study was to determine which histopathologic criterion is more accurate and practical in diagnosing cutaneous LE. Material and Methods: Samples taken from patients with clinical manifestations of Cutaneous LE with pathologic confirmation, included. All patients had direct immuno fluorescent (DIF) samples that recorded. Histopathologic findings are categorized into three groups: group 1 contains epidermal changes, group 2 includes interface changes and group 3 contains dermal changes. Different histopathologic finding such as perivascular infiltration, follicular atrophy, follicular plaque, and basements membrane thickness and other changes, as well as DIF patterns, were recorded in designed questionnaires to further analysis with SPSS software. Results: Of 145 patients (61.4% female and 38.6% male) in 58.6% DLE was the first clinical diagnosis,23% was the second and in subsequent 4.1%, 1.4% and 0.7% was third, fourth and fifth diagnosis respectively. In 11% of caeses DLE was not among clinical impressions. DIF was positive in 49%. As a whole, superficial perivascular and perifolicular infiltration were observed in 99% of the cases and was the commonest pathologic feature followed by basal vacuolization, peri follicular infiltration and epidermal atrophy. Other pathologic changes were observed with variable rates. Discussion: By grouping histopathologic criterion, it seems that hyperkeratosis and thickening of Basement membrane may be major histologic criterion and peri vascular infiltration, peri follicular infiltration and eccrine gland infiltration, may be minor.