Accumulation Of Autoantibodies Research Articles

Changes in the autoantibodies levels to neuroreceptors in the blood serum and brain tissue of rats during chronic administration of bromocriptine

The experiments were carried out on 46 white laboratory male rats Wistar with a body weight of 250–280 g. Animals were daily administered intraperitoneally for 28 days with bromocriptine at a dose of 1 mg/kg and, as a control, physiological saline. In animals treated with bromocriptine, an accumulation of autoantibodies in blood serum and in brain tissue to neuroreceptors was found compared to control animals: NMDA (subunits NR1, NR2A, NR2B) and to dopamine receptors of the first and second types (DR1 and DR2). At the same time, the level of autoantibodies in the brain was significantly lower. High levels of autoantibodies were detected after 2 and 4 weeks from the start of immunization of animals. After completion of the chronic administration of bromocriptine, a high level of autoantibodies persisted 3 and 7 days after the last administration of the drug. 14 days after completion of the injections, the level of autoantibodies in the blood and brain decreased significantly. In the group of rats in which autoantibodies were determined 4 weeks after completion of injections, their level did not differ from the values in control animals. An increase of autoantibodies to the S100B protein was found. The levels of autoantibodies to the S100B protein in the blood serum had a positive moderate relationship with the content of autoantibodies to NR2A, NR2B and DR2 in the brain tissue. At the same time, there were no correlations with the levels of AAT to neuroreceptors in the blood.

Jieduquyuziyin prescription alleviates lupus development via inhibiting neddylation pathway to promote Bim-induced apoptosis of double negative T cells

Ethnopharmacological relevanceJieduquyuziyin prescription (JP) is an empirical prescription approved for application to treat systemic lupus erythematosus (SLE) in hospital within China. Despite the prominent treatment effect of JP clinically, further investigation is imperative to explore its underlying mechanisms. Aim of the studyWe aim to investigate the impact of JP on DN T cell apoptosis in the treatment of SLE and the specific regulation mechanisms. Materials and methodsFirstly, female MRL/lpr mice were treated with JP and the therapeutic efficacy of JP was evaluated via skin lesions, lymphoid organ enlargement, accumulation of autoantibodies and renal function. Then, flow cytometer analysis was performed to evaluate the proportions and the apoptosis of T cell subpopulations. Based on the above results, double-negative (DN) T cells were subjected to proteomic with subsequent differential screening. The expression of Ube2m and Bim was further validated using real-time PCR and Western blot. Subsequently, DN T cells were incubated with JP-contained serum in vitro, and cell apoptosis was quantified using flow cytometry. Additionally, the expression levels of Ube2m, Bim and other associated proteins were also assessed through western blotting. To further clarify whether Ube2m serves as the key target of JP in regulating DN T cell apoptosis, the mice that Ube2m was specific deleted in T cells with spontaneous lupus (Ube2m−/−lpr) were utilized. JP was administered to WTlpr or Ube2m−/−lpr mice, followed by assessment of the lupus condition and DN T cell apoptosis. ResultsJP administration effectively ameliorated the lupus phenotype. Then flow cytometry assay showed that JP treatment enhanced DN T cell apoptosis to reduce their accumulation and restored the immune homeostasis. Proteomic analysis revealed a significant inhibition of Ube2m for JP treatment, which is essential for maintaining homeostasis of DN T cells. Further experiments confirmed that JP treatment effectively downregulated the expression of Ube2m and subsequently upregulated the level of pro-apoptotic protein Bim with decreased Bim degradation. In vitro experiments also confirmed that JP-contained serum significantly facilitated DN T cell apoptosis and reduced DN T cell accumulation by inhibiting Ube2m expression. Furthermore, Ube2m−/−lpr mice were utilized and the impact of JP treatment on the apoptosis of DN T cells was found to be minimal in the absence of Ube2m. Mechanistic investigation reveals that JP exerts its effects by suppressing the expression of Ube2m, subsequently inhibiting CRL-dependent degradation of Bim, and ultimately promoting Bim-induced apoptosis in DN T cells. Furthermore, the blockade of Ube2m in T cells effectively prevents JP-induced apoptosis in DN T cells, underscoring Ube2m as one crucial therapeutic target of JP in mediating DN T cell apoptosis and managing SLE. ConclusionsOur findings indicate that JP treatment effectively restores the homeostasis of DN T cells in SLE by inhibiting Ube2m expression, thereby reducing Bim ubiquitination degradation. This ultimately enhanced DN T cell apoptosis and alleviated lupus phenotype.

Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells is considered as a crucial commander during SLE. Neddylation, a significant type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE is still unknown. Here, we reported that neddylation inactivation with MLN4924, a specific inhibitor of NEDD8-activating enzyme E1 (NAE1), or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells in lupus mice. Then double knockout (KO) lupus-prone mice (Ube2m-/-Bim-/-lpr) were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression. Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression. Clinically, we also found that in SLE patients, the proportion of DN T cells was raised and their apoptosis was reduced. Moreover, compared to healthy groups, SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Altogether, our findings provide the direct evidence about the function of neddylation during lupus, suggesting a promising therapeutic approach for this disease.

Impacts of the A20 protein polymorphism, rs2230926, in human B cells

Abstract Patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), often have skewed B cell population ratios, accumulation of autoantibodies, and an increased amount of proinflammatory cytokines aiding in disease development. Genome-wide association studies (GWAS) have strongly linked polymorphisms in A20, encoded by TNFAIP3, to autoimmune diseases including SLE. A20 functions to inhibit the activation of nuclear factor kappa B (NF-κB) through ubiquitination and deubiquitylation of key signaling proteins and has been extensively studied in epithelial cells in response to TNF. Given the role of autoantibodies in SLE and the importance of NF-κB in regulating B cell fate, the role of SLE linked polymorphisms in A20 and their effects on both the canonical and noncanonical NF-κB pathways in human B cells is poorly understood. Our lab has identified an A20 polymorphism, rs2230926 (F127C), that is enriched in a cohort of African American females with SLE. Herein, we investigate the impact of rs2230926 on B cell function. We employed CRISPR/Cas9 genome-editing and generated a TNFAIP3knockout lymphoblastoid Raji human B cell line. To determine how the polymorphism rs2230926 affects the NF-kB pathway, we re-introduced WT A20, A20-rs2230926, and a truncated version of A20 into the TNFAIP3-KO cell line. Using a combination of qRT-PCR, western blotting, and flow cytometry, we determined how rs2230926 influences the expression of proinflammatory cytokines, response to various B cell stimuli, and ultimately NF-κB activity. Dissecting A20’s role in NF-kB signaling will help to understand the dysfunction and regulation of B cells in autoimmunity. Supported by grants from NIH to CDS (R01 AI148471)

IL-13 determines specific IgE responses and SARS-CoV-2 immunity after mild COVID-19 and novel mRNA vaccination.

After recovery, mild and severe COVID-19 diseases are associated with long-term effects on the host immune system, such as prolonged T-cell activation or accumulation of autoantibodies. In this study, we show that mild SARS-CoV-2 infections, but not SARS-CoV-2 spike mRNA vaccinations, cause durable atopic risk factors such as a systemic Th2- and Th17-type environment as well as activation of B cells responsive of IgE against aeroallergens from house dust mite and mold. At an average of 100 days post mild SARS-CoV-2 infections, anti-mold responses were associated with low IL-13 levels and increased pro-inflammatory IL-6 titers. Acutely severely ill COVID-19 patients instead showed no evidence of atopic reactions. Considering convalescents of mild COVID-19 courses and mRNA-vaccinated individuals together, IL-13 was the predominant significantly upregulated factor, likely shaping SARS-CoV-2 immunity. Application of multiple regression analysis revealed that the IL-13 levels of both groups were determined by the Th17-type cytokines IL-17A and IL-22. Taken together, these results implicate a critical role for IL-13 in the aftermath of SARS-CoV-2 mild infections and mRNA vaccinations, conferring protection against airway directed, atopic side reactions that occur in mildly experienced COVID-19.

Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic Tcell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and Tcells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.

Integrative molecular profiling of autoreactive CD4 T cells in autoimmune hepatitis

In most autoimmune disorders, crosstalk of B cells and CD4 T cells results in the accumulation of autoantibodies. In autoimmune hepatitis (AIH), the presence of anti-soluble liver antigen (SLA) autoantibodies is associated with reduced overall survival, but the associated autoreactive CD4 T cells have not yet been characterised. Herein, we isolated and deeply characterised SLA-specific CD4 T cells in patients with AIH. We used brief exvivo restimulation with overlapping SLA peptides to isolate and phenotype circulating SLA-specific CD4 T cells, and integrative single-cell RNA-seq (scRNA-seq) to characterise their transcriptome and T-cell receptor (TCR) repertoire. Autoreactive TCRs were cloned and used to identify dominant SLA-derived epitopes. SLA-specific CD4 T cells were tracked in peripheral blood through TCR sequencing to identify their phenotypic niche. We further characterised disease-associated peripheral blood T cells by high-content flow cytometry in 42 patients with AIH and 17 controls with non-alcoholic steatohepatitis. Autoreactive SLA-specific CD4 T cells were only detected in patients with anti-SLA autoantibodies and had a memory PD-1+CXCR5-CCR6-CD27+ phenotype. ScRNA-seq revealed their pro-inflammatory/B-helper profile. SLA81-100 and SLA177-204 contain dominant T-cell epitopes. Autoreactive TCR clonotypes were predominantly found in the memory PD-1+CXCR5-CD4 T cells, which were significantly increased in the blood of patients with AIH and supported B-cell differentiation through IL-21. Finally, we identified specific T-cell phenotypes linked to disease activity and IgG level during AIH. We provide a deep characterisation of rare circulating autoreactive CD4 T cells and identify their peripheral reservoir in AIH. We also propose a specific phenotype of autoreactive T cells related to AIH disease activity, which will be essential to track, delineate, and potentially target these pathogenic cells. One principal characteristic of autoimmune hepatitis (AIH), like for many other autoimmune diseases, is the accumulation of autoantibodies produced by B lymphocytes following their interaction with autoreactive CD4 T lymphocytes. In this study, we identified and characterised with high resolution these CD4 T cells. This will be essential to track, delineate, and potentially target them during AIH.

Anti−IL-12/23 p40 antibody attenuates chronic graft-versus-host disease with lupus nephritis via inhibiting Tfh cell in mice

Systemic lupus erythematosus (SLE) is an autoimmune disease that is mainly caused by excessive accumulation of autoantibodies that target autoantibodies such as nucleic acids. T helper (Th) cell have been associated with the development of SLE. Typically, different subsets of Th cells secrete various cytokines to regulate the disease progression. IL-12 and IL-23 participate in the differentiation and activation of multiple Th cell subsets, including Th1, Th2, Th9, Th17, regulatory T (Treg) and follicular helper T (Tfh) cells. Because of the signature p40 subunit shared by IL-12 and IL-23, blocking IL-12/IL-23 signaling may interfere the differentiation of Th cell and directly inhibit the secretion of proinflammatory cytokines. In this study, we examined the effects of anti−IL-12/23 p40 antibody on chronic graft-versus-host disease with lupus nephritis, and found that the therapeutic effectiveness was mediated through the inhibition of Tfh cell in mice. Moreover, anti−IL-12/23 p40 antibody inhibited human Tfh cell differentiation in vitro. These results strongly suggest that Tfh cell contribute to the pathogenesis of SLE, and the neutralization of IL-12/IL-23 signaling during Tfh cell differentiation may be critical for the treatment of SLE.

Hypergammaglobulinemic purpura of Waldenström in children.

Hypergammaglobulinemic purpura of Waldenström (HGPW), a rare cutaneous eruption characterized by the triad of recurrent episodes of lower extremity petechiae, symptoms of stinging and burning, and lower extremity edema, is poorly described in children. Some children have been reported to follow a benign course, while others are eventually diagnosed with fulminant rheumatologic disease. To determine the distinguishing features of HGPW including the spectrum of disease manifestations and clinical outcomes. This is a multicenter, retrospective case series of six children with HGPW combined with a literature review of 45 previously published pediatric cases. Most children were eventually diagnosed with systemic disease (63%) or developed autoantibody accumulation suggestive of evolving disease (71%). The most common diagnoses were Sjogren's syndrome and systemic lupus erythematosus. The mean duration between onset of cutaneous eruption and diagnosis of systemic disease was 5.6years, underscoring that HPGW patients often present with a rash that precedes the development of systemic symptoms. Diagnosis of HGPW should prompt initial screening for rheumatologic disease with long-term rheumatology follow-up, as the majority of patients present with evolving manifestations of systemic disease.

Proteases in Pemphigoid Diseases.

Pemphigoid diseases are a subgroup of autoimmune skin diseases characterized by widespread tense blisters. Standard of care typically involves immunosuppressive treatments, which may be insufficient and are often associated with significant adverse events. As such, a deeper understanding of the pathomechanism(s) of pemphigoid diseases is necessary in order to identify improved therapeutic approaches. A major initiator of pemphigoid diseases is the accumulation of autoantibodies against proteins at the dermal-epidermal junction (DEJ), followed by protease activation at the lesion. The contribution of proteases to pemphigoid disease pathogenesis has been investigated using a combination of in vitro and in vivo models. These studies suggest proteolytic degradation of anchoring proteins proximal to the DEJ is crucial for dermal-epidermal separation and blister formation. In addition, proteases can also augment inflammation, expose autoantigenic cryptic epitopes, and/or provoke autoantigen spreading, which are all important in pemphigoid disease pathology. The present review summarizes and critically evaluates the current understanding with respect to the role of proteases in pemphigoid diseases.

CTLA-4 regulates T follicular regulatory cell differentiation and participates in intestinal damage caused by spontaneous autoimmunity

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a co-inhibitory molecule expressed by T cells and is required for immune regulation and inflammation prevention. In clinical patients, the CTLA-4 mutation causes spontaneous immune-related early-onset Crohn's disease; however, its potential mechanism is still unknown. In the current study, we found that defects in CTLA-4 in CD4 cells lead to limited differentiation of T follicular regulatory (Tfr) cells and relatively increased T follicular helper (Tfh) cells and spontaneous B cell germinal centres (GCs) responses that trigger the accumulation of autoantibodies in intestinal epithelial cells. In addition, the deficiency of Tfr cells caused by defects in CTLA-4 causes these cells to lose their function of inhibiting the non-specific immune response produced during the specific humoural immune response induced by MCMV (mouse cytomegalovirus), resulting in acute intestinal injury and death in mice. The lack of Tfr cells may be responsible for the immunosuppressive disorder of inflammatory bowel disease caused by CTLA-4 deficiency. In conclusion, we verified that CTLA-4 may be required for Tfr cell differentiation and production. Tfr cells inhibit B cell responses and prevent humoural autoimmune-mediated intestinal damage by regulating Tfh-dependent GC responses.

Strength in Numbers: Opportunities for Enhancing the Development of Effective Treatments for Type 1 Diabetes-The TrialNet Experience.

The early to mid-1980s were an inflection point in the history of type 1 diabetes research. Two landmark events occurred: the initiation of immune-based interventions seeking to prevent type 1 diabetes and the presentation of an innovative model describing the disorder's natural history. Both formed the basis for hundreds of subsequent studies designed to achieve a dramatic therapeutic goal-a means to prevent and/or reverse type 1 diabetes. However, the need to screen large numbers of individuals and prospectively monitor them using immunologic and metabolic tests for extended periods of time suggested such efforts would require a large collaborative network. Hence, the National Institutes of Health formed the landmark Diabetes Prevention Trial-Type 1 (DPT-1) in the mid-1990s, an effort that led to Type 1 Diabetes TrialNet. TrialNet studies have helped identify novel biomarkers; delineate type 1 diabetes progression, resulting in identification of highly predictable stages defined by the accumulation of autoantibodies (stage 1), dysglycemia (stage 2), and disease meeting clinical criteria for diagnosis (stage 3); and oversee numerous clinical trials aimed at preventing disease progression. Such efforts pave the way for stage-specific intervention trials with improved hope that a means to effectively disrupt the disorder's development will be identified.

The non-haemostatic role of platelets in systemic lupus erythematosus.

Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity. Through a broad repertoire of receptors, platelets respond promptly to immune complexes, complement and damage-associated molecular patterns, and represent a major reservoir of immunomodulatory molecules in the circulation. Furthermore, evidence suggests that platelets are activated in patients with SLE, and that they could contribute to the circulatory autoantigenic load through the release of microparticles and mitochondrial antigens. Herein, we highlight how platelets contribute to the immune response and review evidence implicating platelets in the pathogenesis of SLE.

Exceptional Diversity of Catalytic Antibodies with Varying Activity in the Blood of Autoimmune and Viral Disease Patients

Antibodies (ABs) that target autoantigens were more abundant in the blood of humans and animals suffering from certain autoimmune and viral diseases than in the blood of healthy donors. The emergence of ABs with diverse types of catalytic activity is among the earliest manifestations of certain autoimmune diseases. The putative mechanisms that underlie the accumulation of autoantibodies and abzymes in different autoimmune diseases are addressed in the present review. The extraordinary diversity of abzymes with various types of catalytic activity is discussed.

Role of the TNF-family cytokine TL1A and its receptor DR3 in systemic autoimmunity and glomerulonephritis

Abstract DR3 (Tnsfrsf25) is a death domain-containing tumor necrosis factor receptor found primarily on activated T cells and innate lymphocytes. Interaction with its ligand the TNF-family cytokine TL1A plays critical roles in diverse autoimmune disease models in facilitating T cell accumulation at the site of inflammation while the systemic response was unaffected. To determine whether DR3 could play a role in systemic autoimmunity, we studied the role of DR3 in the MLR/lpr mouse model of lupus. Lpr mice have a mutation in the TNF family receptor Fas (CD95, Tnfrsf6) that impair its expression, causing a systemic autoimmune disease that mimics systemic lupus erythematosus (SLE) observed in humans. DR3 deficient lpr mice developed identical degrees of lymphadenopathy, splenomegaly compared to control littermates. Accumulation of autoantibodies was also not dependent on DR3. However, DR3 deficiency significantly protected MRL/lpr mice from IgG and C3 glomerular immune complex deposition and DR3 deficient kidneys had decreased medullary T cell accumulation, decreased periglomerular and medullary macrophage infiltrates, reduced proteinuria and reduced renal pathology. In addition, DR3-deficient CD4+ T cell transfer in a chronic graft-versus-host disease (GVHD) model showed similar levels of autoantibodies and immunoglobulin class switching than with wild-type CD4+ T cells but decreased proteinuria and reduced renal pathology. These findings show that DR3 specifically promotes renal pathology in the MRL/lpr mouse model of lupus nephritis and in chronic GVHD without affecting systemic autoimmunity. Blockade of TL1A-DR3 interactions may be a novel strategy to counter nephritis and other organ damage in human SLE.

Dysregulation of T helper-type cytokines appears prior to and concurrent with appearance of autoantibody specificities during early SLE pathogenesis and contributes to prognosis of transition to classified disease

Abstract Autoantibodies and immune dysregulation are associated with systemic lupus erythematosus (SLE), but how these factors influence disease development is unknown. This study evaluates timing and changes in SLE-linked autoantibodies and soluble mediator pathways in the years preceding SLE classification. Serial sera from 84 SLE cases spanning pre- and post-SLE classification (average time = 5.98 years) and matched healthy controls (HC) were obtained from the Department of Defense Serum Repository. Adjusting for multiple comparison, a number of soluble mediators, including IL-5 (q=4.35×10−6), IL-6 (q=8.26×10−6), and IFN-γ (q=0.037), were significantly elevated in cases vs. HC >3.5 years pre-classification, prior to (IL-5 and IL-6) and concurrent with (IFN-γ) the earliest SLE-specific autoantibody specificity, anti-Ro/SSA. Th1-type, Th17-type, and TNF superfamily soluble mediators increased longitudinally in cases approaching SLE classification, but not in HC (q<0.05). In particular, serum levels of BLyS and APRIL were comparable in cases and HC until <10 months pre-classification (q=0.003 and q=0.019, respectively). Random forest models incorporating IL-5, IL-6, and IFN-γ levels (79–82% accuracy) distinguished future SLE patients better than models with ANA alone (58% accuracy) >3.5 years before classification. These data indicate that pre-clinical immune system perturbations allow for the accumulation of autoantibodies preceding clinical symptoms and SLE classification.

Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification

ObjectivesThe relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type...

Anti-Neutrophil Antibodies (ANCA) Level in Psoriatic Patients with Different Degree of Severity

Psoriasis is a chronic, autoimmune skin disease with cutaneous manifestations; association of several factors including environmental, genetics and immunological abnormalities with psoriasis is documented.
 The acronym ANCA (Anti-Neutrophil Cytoplasmic Autoantibodies) is defined by an accumulation of autoantibodies with specificity against different granulocytic, monocyte and probably endothelial cytoplasmic antigens include (elastase, lactoferrin, lysozyme and Cathpsin G ), are most commonly found in systemic vasculitis, necrotizing vasculitis and in active generalized wegener's granulomatosis.
 The objective of this study is to assess the anti-neutrophil antibody level (ANCA) as inflammatory markers in patients with psoriasis with different degree of severity, correlate the results with the degree of severity and compare the level of these antibodies with those of control group. 
 This study was conducted from Feb. 2014 to Feb. 2015, blood samples were collected from thirty two persons attending to Al-Karama Teaching Hospital, Baghdad Teaching Hospital and private clinics, sixteen of them having psoriasislabelled as study groups and the rest were free of the disease labelled as control group. The psoriatic patients were classified into three groups according to the degree of severity of the disease as mild (four patients), moderate (four patients) and sever (eight patients), the Psoriasis Area Severity Index (PASI) were used to assess the severity of the disease. Thepatient’sgroup distributed as male (31.2%) and female (62.8%), the serum level of ANCA antibody was measured in thepatient’s serum of different degree of severity and in control group by using EnzymeLinked Immunosorbent Assay technique (ELISA) in laboratory of Al-karama Teaching Hospital.
 The results proved that the serum levels of ANCA in psoriatic patients were significantly higher than that of control group in all degree of disease severity when ANOVA test used to analyze the data, also the results reported that the level of anti- elastase and ant-lactoferrin were significantly higherin sever degree group of psoriatic patients than mild and moderate degree groups (p≤0.05)when tested by LSD test, no significant difference was noted between mild and moderate degree groups (p >0.05).
 From that we can conclude that autoantibodies against neutrophil antigens are generally associated with inflammatory psoriatic disorder; In addition, the autoantibodies levels were related to the degree of severity of the disease especially antielastase and antilactoferrin

T cell epitopes and post-translationally modified epitopes in type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease in which progressive loss of self-tolerance, evidenced by accumulation of auto-antibodies and auto-reactive T cells that recognize diverse self-proteins, leads to immune-mediated destruction of pancreatic beta cells and loss of insulin secretion. In this review, we discuss antigens and epitopes in T1D and the role that post-translational modifications play in circumventing tolerance mechanisms and increasing antigenic diversity. Emerging data suggest that, analogous to other autoimmune diseases such as rheumatoid arthritis and celiac disease, enzymatically modified epitopes are preferentially recognized in T1D. Modifying enzymes such as peptidyl deiminases and tissue transglutaminase are activated in response to beta cell stress, providing a mechanistic link between post-translational modification and interactions with the environment. Although studies of such responses in the at-risk population have been limited, current data suggests that breakdown in tolerance through post-translational modification represents an important checkpoint in the development of T1D.

Dysregulation of type II interferon associated mediators precedes autoantibody accumulation and type I interferon elevation and predicts transition to systemic lupus erythematosus classification (BA3P.109)

Abstract Autoantibodies and interferon (IFN) are associated with clinical illness in systemic lupus erythematosus (SLE), but how these factors influence autoimmune disease development is unknown. This study evaluates the timing and changes in SLE-linked autoantibody specificities, serum IFN-α activity, and IFN-associated soluble mediator levels in the years preceding SLE classification. Serial sera from 55 SLE cases spanning pre- and post-SLE classification (average time = 4.3 years) and matched healthy controls (HC) were obtained from the Department of Defense Serum Repository. Cases with positive serum IFN-α activity had more SLE-linked autoantibody specificities (p<0.05). Growth curve modeling and path analysis corroborated that most autoantibody specificities precede IFN-α activity, and IFN-γ and IP-10 were elevated prior to or concurrent with autoantibody positivity (p<0.01). The number of autoantibody specificities and IFN-associated soluble mediators, as well as female gender, predicted increases in IFN-α activity (p<0.04; ANCOVA). IFN-γ and MCP-3 levels, as well as the presence of anti-chromatin and spliceosomal autoantibodies, best predicted transition to SLE with 93% accuracy >4 years before SLE classification (Random Forest). These data indicate that pre-clinical immune system perturbations allow for the accumulation of autoantibodies and subsequent elevation in IFN-α activity immediately preceding clinical symptoms and SLE classification.