Serum Levels Of Antinuclear Antibodies Research Articles

Immune cell alterations in a pristane‐induced lupus model in C57BL/6J mice

AbstractBackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune‐mediated inflammation affecting multiple organs and systems. The aim of this study was to establish and validate a pristane‐induced SLE model in C57BL/6J mice and analyze immune cell alterations.MethodsSix‐week‐old female C57BL/6J mice were randomly assigned to two groups (n = 6 per group). The pristane group received a single 0.5 mL intraperitoneal injection of pristane, whereas the control group received a single intraperitoneal injection of 0.5 mL saline. Urine samples were collected before injection and at 2, 4, and 6 months after injection to monitor urinary protein levels. Six months postinjection, the mice were euthanized, and serum, kidney, and spleen tissues were collected. Serum antinuclear antibody (ANA), double‐stranded DNA(dsDNA), and inflammatory cytokine levels (interleukin [IL]‐1β, IL‐6, tumor necrosis factor‐α) were quantified by enzyme‐linked immunosorbent assay. Histological alterations in kidney tissues were assessed using hematoxylin and eosin, periodic acid‐Schiff, Masson, and silver staining, in addition to direct immunofluorescence for immunoglobulin G and complement component 3. Flow cytometry was used to assess immune cell alterations in the spleen.ResultsFollowing the intraperitoneal injection of pristane, the mice exhibited a gradual increase in spleen size, body weight, and urinary protein levels. Serum levels of ANA, dsDNA, and inflammatory cytokines were elevated to varying degrees (p < 0.05). Histological analysis of the kidney sections revealed characteristic nephritic alterations, including glomerular swelling and lymphocyte infiltration. In the spleen, T cell numbers decreased, whereas the proportion of myeloid cells significantly increased, particularly monocytes, neutrophils, and macrophages (p < 0.05).ConclusionPristane successfully induced a SLE model in C57BL/6J mice, characterized by nephritic injury and significant alterations in immune cell populations.

Correlation between the existence of serum autoantibodies and the risk of endometriosis: A systematic review and meta-analysis.

Endometriosis is a common condition among women and can cause complications such as abdominal pain, dysmenorrhea, and infertility. One of the potential causes of this disease is autoimmunity. However, evidence regarding the role of autoimmunity is conflicting and inconclusive. The aim of this study was to investigate whether autoantibodies, a sign of autoimmunity, are present in people suffering from endometriosis. Relevant studies up to April 14, 2023 were identified by systematically searching Scopus, PubMed, Web of Science, Embase, and Google Scholar. This meta-analysis includes all qualified case-control studies of human populations that analyzed the association between serum autoantibodies and endometriosis. The odd ratios and 95% confidence intervals were calculated. In addition, heterogeneity and publication bias were examined, and subgroup analyses were performed based on region and target antigens. Forty-one studies were included, comparing 2,825 endometriosis patients with 4,158 healthy controls. The meta-analysis findings indicated a significant association between the presence of autoantibodies in the serum and an increased susceptibility to endometriosis (odds ratio: 4.242, confidence interval 95%: 3.824-4.706, p<0.001). In addition, there was a significant correlation between the presence of endometriosis and serum levels of anti-nuclear antibodies, B2 glycoprotein 1, CA125, carbonic anhydrase 1, cardiolipin, endometrial, laminin-1, smooth muscle, and syntaxin autoantibodies. Upon further analysis, it was found that the serum levels of these autoantibodies were higher in patients with endometriosis from North America than in those from other regions (p=0.001). The study revealed a significant correlation between serum autoantibodies and susceptibility to endometriosis, highlighting autoimmunity as a potential cause.

The Diagnostic Value of ANA and Anti-SMA in Suspected Patients with Autoimmune Hepatitis

BACKGROUND: Autoimmune hepatitis (AIH) is an unknown chronic disease characterized by hepatocellular inflammation with a tendency to progress to cirrhosis. AIH can present with symptoms of acute hepatitis with symptoms of chronic liver disease. AIH occurs globally; it is more commonly found in females. Autoantibodies such as antinuclear, smooth muscle, liver kidney microsome, and soluble liver antigen are used to aid in the diagnosis of AIH, which presents with a variety of symptoms that also contribute to the classification of AIH. AIM: Evaluation of anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (SMA) positivity in hepatic diseases, gastrointestinal diseases, viral hepatitis, and extra-hepatic diseases, providing better markers for the early diagnosis of AIH-type 1. MATERIALS AND METHODS: The study included 207 individuals. 62.4% of them were female. Regarding the diagnoses, we grouped them into 4 groups: hepatic diseases (n = 73), viral hepatitis B and C (n = 54), gastrointestinal diseases (n = 34), and extra-hepatic diseases (n = 46). Serum levels of ANA and anti-SMA were measured using an indirect immunofluorescence method following the manufacturer’s instructions (Aesku Diagnostics, Germany). Fluorescence intensity was interpreted semi-quantitatively based on negative control (0) and positive control (+4). RESULTS: The positivity of ANA and anti-SMA resulted as follows: In hepatic diseases 34.2% and 48%, in viral hepatitis B and C, ANA positivity was 14.8% and SMA positivity was 22.2%; in gastrointestinal diseases, ANA and SMA positivity were, respectively, 11.8% and 20.6%; and in extrahepatic diseases, positivity of ANA resulted in 32.6% and SMA in 26%. When compared to the viral hepatitis patient group, the ANA specificity for hemagglutination inhibition (HAI) was 85.2% and that of anti-SMA was 77.8%. The analysis of 46 extrahepatic patient groups provided an ANA specificity of 67.4% and an anti-SMA specificity of 74% for HAI. The comparison to gastrointestinal disease showed that ANA specificity for HAI was 88.2% and anti-SMA specificity was 79.4%. CONCLUSION: Diagnosing AIH is difficult because the clinical spectrum ranges from an asymptomatic presentation to an acute and severe disease. So in all cases, AIH must be suspected. Both males and females can develop AIH, but the disease is more common in females. Based on our diagnostic parameters, we can say that ANA and anti-SMA provide moderate sensitivity for AIH, but they are more specific to AIH type 1.

EFFECTS OF DIET ON CCL11 EXPRESSION AND AGING OF LUNGS AND TESTES OF MICE

Aging is a complex phenomenon symbolized by dynamic loss of tissue homeostasis with diminished cellular function. Along with genetic factors, many epigenetic factors as such lifestyle of an individual also affects aging. The aim of this study was to check the effect of different food habits in the process of aging using an aging biomarker CCL11. An increase in expression of CCL11 was observed in carbohydrate and fat rich foods groups. However, no effect on CCL11 expression was seen in calorie restricted diet groups. Mice fed with carbohydrates rich food gained weight, showed high levels of glucose, HDL and triglycerides while consumption of fat rich food in mice raised serum levels of anti-nuclear antibodies and LDL comparing to the control groups. Different food habits affected differently the serum levels of glucose, anti-nuclear antibodies, and lipid profile. H and E staining of testis and lungs showed that consumption of fat rich food caused emphysema, epithelial degeneration of lungs and aspermatogenesis in testes. Moreover, Calorie restricted diet showed vacuolization in testis. This study shows that food influence aging, expression levels of CCL11, physiology and morphology of lungs and testes in mice. Key words: Aging, CCL11, epigenetic factor, aspermatogenesis, dietary habits

Targeting of EIF4EBP1 by miR-99a-3p affects the functions of B lymphocytes via autophagy and aggravates SLE disease progression.

Excessive activation of immune cells plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of immune cells by miRNAs is a research hotspot. In this study, second‐generation high‐throughput sequencing revealed a reduction in miR‐99a‐3p expression in patients with SLE; however, the specific mechanism underlying this phenomenon remains unclear. After transfection with an miR‐99a‐3p agomir, the proliferation of Ball‐1 cells decreased and the levels of their apoptosis increased. The opposite effects were observed in cells transfected with the miR‐99a‐3p antagomir. Luciferase reporter assay indicated that miR‐99a‐3p directly targeted EIF4EBP1. Rescue experiments confirmed the proposed interaction between miR‐99a‐3p and EIF4EBP1. In vitro, in vivo and clinical investigations further confirmed that the miR‐99a‐3p agomir reduced the expression of EIF4EBP1, LC3B and LAMP‐2A. In the in vivo experiments, serum levels of anti‐nuclear antibodies, double‐stranded DNA, IgE, IgM, IL‐6, IL‐10 and B lymphocyte stimulator were higher in mice from the antagomir group than those in mice from the MRL/lpr group. Furthermore, the protein and mRNA levels of EIF4EBP1, LC3B and LAMP‐2A, the intensity of immunohistochemical staining of EIF4EBP1, LC3B and LAMP‐2A, the urinary protein levels, and the C3 immunofluorescence deposition increased in mice from the antagomir group. The upregulation of miR‐99a‐3p expression protected B cells from EIF4EBP1‐mediated autophagy, whilst the downregulation of miR‐99a‐3p expression induced autophagy via the EIF4EBP1‐mediated regulation of the autophagy signalling pathway in B cells isolated from individuals with SLE. Based on these results, miR‐99a‐3p and EIF4EBP1 may be considered potential targets for SLE treatment.

Differences in autoimmunity factors based on the activity of thromboangiitis obliterans.

The treatment of Buerger's disease (BD) presents a medical problem as its etiology is still unclear. In this study, our objective was to evaluate the serum levels of autoimmune markers in patients with different clinical features of BD. In this study, 80 BD patients were categorized in three groups using a cross-sectional design: migratory thrombophlebitis, cold sensitivity, and skin discoloration (mild symptoms); chronic ulcers, claudication, and burning pain of the feet at night (moderate symptoms); pain at rest and spontaneous gangrene (severe symptoms). Enzyme-linked immunosorbent assay was performed to measure antibodies against immunoglobulin M rheumatoid factor (IgM RF), anti-nuclear antibodies (ANA), antibodies against cyclic citrullinated peptide (anti-CCP), antiphospholipid antibodies (APA), anti-cardiolipin antibodies (ACLA), anti-double stranded DNA (anti-dsDNA), and extractable nuclear antigen (ENA) profile. Patients with severe symptoms showed the lowest age (p=0.031), ESR (p<0.001), and highest prevalence of ischemia (p<0.001). In all the patients, the serum levels of ANA and IgM RF were higher than 1 U and 15 IU/mL, respectively. However, the progression of the disease from mild to moderate did not affect these markers significantly (p>0.05). Other markers were negative in patients with BD. The findings of this study indicate that BD may closely be correlated to transient autoimmune phenomena, despite the fact that further research is required to investigate how transient unspecific autoimmune reactions contribute to the BD pathogenesis.

Seroprevalence of antinuclear antibodies, antibrucella antibodies, and hepatitis B surface antigen in women with recurrent abortion

Background: Recurrent abortion is a globally common problem. Many factors play a crucial role in the pathogenesis of abortion such as antinuclear antibodies (ANA), antibrucella antibodies and hepatitis B surface antigen (HBsAg). Objectives: The study objective was to estimate the serum levels of antinuclear antibodies (ANAs), antibrucella antibodies, and hepatitis B surface antigen among recurrent aborting women. Materials and Methods: One hundred and twenty women were enrolled in this prospective case–controlled study from Maternity Hospital, Erbil City, Iraq. The study included sixty patients with a history of three and more attacks of previous abortions and sixty healthy pregnant women. All were screened for ANA-IgG, antibrucella antibodies, and hepatitis B surface antigen (HBsAg) in serum. Results: It was noted that 15/60 (25%) patients and 6/60 (10%) healthy controls were positive for ANA-IgG with a mean concentration of 6.2 ± 0.4 IU/ml in the patient group and 0.75 ± 0.325 IU/ml in the healthy controls with statistical significance at P ≤ 0.05. The distribution for ANA with antibrucella and HbsAg in patient group was as follows: 12/15 (80%) and 6/15 (46.15%), respectively, among the seropositive ANA patients with a high significance atP

Serological markers of autoimmunity ‎in women with polycystic ovary ‎syndrome

In the present study, we evaluate the serum level of common autoimmunologic markers in ‎women with polycystic ovary syndrome (PCOS) and study their relationship with ‎hormonal ‎parameters. The study was ‎an observational case-control study, done in a Tertiary referral hospital, the study ‎included ‎50 women with polycystic ovary syndrome and 50 matched control.‎ Serum levels of Antinuclear Antibody (ANA) and anti-double-stranded DNA (dsDNA) were significantly higher in polycystic ovary ‎syndrome women compared to control. Also, luteinizing hormone (LH), follicle stimulating hormone (FSH), and LH/FSH ratio were ‎significantly higher in polycystic ovary syndrome women compared to control. ‎dsDNA had excellent ability to differentiate PCOS from control (AUC=0.901) while ANA had good discrimination ability ‎‎(AUC=0.809). There was a significant direct relationship between ANA, dsDNA, and TSH ‎with FSH in PCOS women, ‏also a ‎significant direct relationship between ANA and TSH with LH, while ‎DsDNA did not correlate with LH. In conclusion, there is a clear relationship between immunological markers (ANA, dsDNA) with ‎‎polycystic ovary syndrome in various components of the disease, dsDNA offer better ability than ANA as a predictor of PCOS, indicating that dsDNA can be used as a non-invasive diagnostic tool for PCOS.

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8–12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Inflammatory arthritis in pediatric patients with morphea.

Morphea or localized scleroderma is an inflammatory disorder resulting in fibrosis of the skin and subcutaneous tissues. Joint contractures, arthralgias, and functional compromise are recognized associations of pediatric morphea. The co-existence of inflammatory arthritis and morphea is not well-described in the literature. To investigate the relationship between pediatric morphea and inflammatory arthritis with regards to cutaneous, musculoskeletal, and laboratory findings and treatment regimens. A systematic retrospective chart review of 53 patients with pediatric morphea was performed and analyzed for morphea subtypes, arthritic joint involvement, serum autoantibodies, and therapeutic interventions. Eleven out of 53 patients had polyarthritis that involved joints unrelated to the site of the cutaneous morphea. These patients were mostly girls with either the linear or generalized subtypes of morphea. Serum levels of antinuclear antibodies were more significantly elevated in patients with arthritis. All children were treated with methotrexate in addition to other systemic or topical immunosuppressive agents. This was a small, single-center retrospective study. Pediatric morphea co-existed with inflammatory arthritis in 11 of 53 children. Further understanding and appreciation of this relationship may direct more intensive therapy and musculoskeletal screening.

Serologic markers of autoimmunity in women with recurrent pregnancy loss.

Various autoimmunologic mechanisms have been shown to be involved in recurrent pregnancy loss (RPL). This study aimed to evaluate whether women with RPL have elevated serum levels of common autoimmunologic parameters. Serum levels of antinuclear antibodies (ANAs) were measured in 114 women with RPL, and 107 healthy controls using a qualitative immunometric enzyme immunoassay, serum levels of IgG class autoantibodies against histone, IgG class autoantibodies against nucleosomes, and IgG class autoantibodies against double-stranded (ds) DNA were measured by quantitative enzyme immunoassays. No differences were ascertained regarding serum levels of ANAs (P=.9), serum levels of antibodies against histones (P=.1), antibodies against nucleosomes (P=.4) and antibodies against dsDNA (P=.6) between women with RPL and healthy controls. No associations were found between serum levels and clinical characteristics of affected women. Our study shows that serologic parameters of autoimmunity are not elevated in women with RPL and are not associated with clinical characteristics of affected women.

Serum Antinuclear Antibodies as Indicator of Relapse in Patients with Non- Hodgkins Lymphoma

Background: The association of antinuclear antibodies (ANA) has been reported in Non-Hodgkin’s lymphoma (NHL). This study was conducted to assess the serum levels of ANA in NHL patients and its relationships with prognosis. Subjects and methods: This study included 64 patients with NHL and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum levels of ANA. Results: There were significant differences in the serum ANA between NHL patients and controls (P 0.8 (AUC: 0.876). Conclusion: Our data argue that positive ANA levels can be useful for diagnosis of relapse in NHL patients.

Innate Immune Signaling Induces IL-7 Production, Early Inflammatory Responses, and Sjögren's-Like Dacryoadenitis in C57BL/6 Mice.

Innate immune signaling elicited by polyinosinic-polycytidylic acid (poly I:C) induces IL-7 production and early inflammatory responses in the salivary gland and accelerates the development of Sjögren's syndrome (SS)-like sialadenitis. Whether poly I:C can induce similar responses in the lacrimal gland (LAC) has not been characterized. In this study, we examined the early responses and pathologic changes of the LAC tissue in response to poly I:C treatment. Poly I:C or recombinant human IL-7 was injected intraperitoneally into C57BL/6 mice, and the LAC was harvested at different time points. Expression of chemokines and cytokines in the LAC was measured by RT-PCR, immunofluorescence staining, and immunohistochemistry. Leukocytic infiltration and caspase-3 activation were analyzed by hematoxylin and eosin staining and immunohistochemistry. Serum antinuclear antibody levels were also determined. Tear secretion was measured by phenol red cotton threads. Administration of poly I:C induced IL-7 gene expression and protein production in the LAC. Poly I:C also induced the expression of CXCR3 ligands, monocyte chemoattractant protein-1, IL-23p19, and TNF-α in the LAC in an IL-7-dependent fashion. Similarly to poly I:C, administration of exogenous IL-7 also up-regulated these proinflammatory mediators. Furthermore, repeated administration of poly I:C to C57BL/6 mice over an 8-day period caused leukocytic infiltration and caspase-3 activation in the LAC, antinuclear antibody production, and impaired tear secretion. Poly I:C induces IL-7 production, early inflammatory responses, and characteristic pathologies of SS-like dacryoadenitis in non-autoimmune-prone C57BL/6 mice. These findings provide new evidence that viral infection-elicited innate immune signaling may be one of the early triggers of SS-like dacryoadenitis.

Prednisone treatment inhibits the differentiation of B lymphocytes into plasma cells in MRL/MpSlac-lpr mice.

A number of evidence shows that the differentiation of B lymphocytes into plasma cells plays an important role in lupus pathogenesis. In this study we investigated how prednisone, a classical therapeutic drug for autoimmune diseases, regulated plasma cell differentiation in MRL/MpSlac-lpr mice. MRL/lpr mice were treated with prednisone (2.5 or 5 mg·kg(-1)·d(-1), ig) for 13 weeks, and the proteinuria levels and survival times were monitored. After the mice were euthanized, blood sample, spleen and thymus were collected. The serum levels of anti-dsDNA antibody, anti-nuclear antibody, IL-21, and IL-10 were detected using ELISA kits. Subsets of splenic B and T lymphocytes were quantified with flow cytometry. Transcription factor Blimp-1 and Bcl-6 expression was determined using qPCR and Western blot. Prednisone treatment dose-dependently attenuated the lupus symptoms in MRL/lpr mice with decreased proteinuria levels, prolonged survival times, decreased serum anti-nuclear antibody levels, and reduced spleen and thymus indices. Prednisone treatment also significantly decreased the elevated percentages of plasma cells and plasma cell precursors, decreased the percentages of activated T cells, and increased the frequency of CD4(+)CD62L(+) cells, demonstrated that decreased anti-nuclear antibodies and improvements in lupus symptoms were associated with decreased plasma cells. Furthermore, prednisone treatment decreased serum IL-21 and IL-10 levels and reduced the expression of splenic Blimp-1 and Bcl-6 (two key regulatory factors for plasma cell differentiation) in MRL/lpr mice. Prednisone treatment restricts B lymphocyte differentiation into plasma cells in MRL/lpr mice, which may be correlated with the inhibition of IL-21 production and the restoration of the balance between Blimp-1 and Bcl-6.

CD47 deficiency ameliorates autoimmune nephritis in Faslpr mice by suppressing IgG autoantibody production

CD47, a self-recognition marker, plays an important role in both innate and adaptive immune responses. To explore the potential role of CD47 in activation of autoreactive T and B cells and the production of autoantibodies in autoimmune disease, especially systemic lupus erythematosus (SLE), we have generated CD47 knockout Fas(lpr) (CD47(-/-) -Fas(lpr) ) mice and examined histopathological changes in the kidneys, cumulative survival rates, proteinuria, extent of splenomegaly and autoantibodies, serum chemistry and immunological parameters. In comparison with Fas(lpr) mice, CD47(-/-) -Fas(lpr) mice exhibit a prolonged lifespan and delayed autoimmune nephritis, including glomerular cell proliferation, basement membrane thickening, acute tubular atrophy and vacuolization. CD47(-/-) -Fas(lpr) mice have lower levels of proteinuria, associated with reduced deposition of complement C3 and C1q, and IgG but not IgM in the glomeruli, compared to age-matched Fas(lpr) mice. Serum levels of antinuclear antibodies and anti-double-stranded DNA antibodies are significantly lower in CD47(-/-) -Fas(lpr) than in Fas(lpr) mice. CD47(-/-) -Fas(lpr) mice also display less pronounced splenomegaly than Fas(lpr) mice. The mechanistic studies further suggest that CD47 deficiency impairs the antigenic challenge-induced production of IgG but not IgM, and that this effect is associated with reduction of T follicular cells and impairment of germinal centre development in lymphoid tissues. In conclusion, our results demonstrate that CD47 deficiency ameliorates lupus nephritis in Fas(lpr) mice via suppression of IgG autoantibody production.

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus.

Systemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Fas(lpr) lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyte-infiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220(+) CD4(-) CD8(-) T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRL-Fas(lpr) lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis.

CD47 deficiency ameliorates autoimmune nephritis in Faslpr mice via suppressing IgG autoantibody production (THER5P.912)

Abstract CD47, a self-recognition marker, significantly regulates both innate and adaptive immune response. To explore the potential role of CD47 in activation of autoreactive T and B cells and the production of autoantibodies in diseases such as systemic lupus erythematosus, we generated CD47-knockout in spontaneous lupus mice (Faslpr). In comparison with Faslpr mice, CD47-/--Faslpr mice exhibited a prolonged lifespan, with no apparent signs of autoimmune nephritis including glomerular cell proliferation, acute tubular atrophy and vacuolization. CD47-/--Faslpr mice had lower level of proteinuria, lower deposition of C3 and C1q in the glomeruli and lesser pronounced splenomegaly compared to the age-matched Faslpr mice. Serum levels of antinuclear antibodies and anti-double-stranded DNA antibodies in CD47-/--Faslpr mice were also significantly reduced. The mechanistic studies further suggested that CD47 deficiency might impair the antigenic challenge-induced production of mouse high affinity IgG but not IgM through reducing T follicular cell production, which results in an impaired formation of germinal centers in lymph tissue. In conclusion, our results demonstrate for the first time that CD47 deficiency ameliorates lupus nephritis in Faslpr mice via suppressing IgG autoantibody production.

Anti-M&amp;lt;sub&amp;gt;3&amp;lt;/sub&amp;gt; Muscarinic Acetylcholine Receptor Antibodies in Systemic Lupus Erythematosus

Background: Evidences have shown that anti-M3 muscarinic acetylcholine receptor IgG (anti-M3 mAChR IgG) are clinically useful autoantibody that exert a cholinergic pharmacologic effect binding and interacting with M3 mAChR at the level of exocrine gland (salivary and ocular). Aims: The aim of this study was to determine the associations between serum level of anti-M3 mAChR IgG in patients with systemic lupus erythematosus (SLE) and other autoantibodies, serum prostaglandin E2 (PGE2), and clinical manifestations. Methods: Serum autoantibodies against M3 mAChR synthetic peptide were measured by enzyme-linked immuno absorbent assay (ELISA) using, as an antigen, a 25-mer peptide K-R-T-V-P-D-N-Q-C-F-I-Q-F-L-S-N-P-A-V-T-F-G-T-A-I corresponding to the amino acid sequence of the second extracellular loop of the human M3 mAChR. Serum levels of antinuclear antibodies (ANA), anti-Smith (Sm) antibodies, anti-phospholipid (APL) antibodies, and PGE2 were determined by ELISA in patients with SLE. Results: We found significantly enhanced titers of anti-M3 mAChR IgG in sera from SLE patients compared with healthy individuals (control). In addition, serum levels of PGE2 were significantly higher in SLE patients than in control patients and were significantly higher in active than in non-active SLE. No correlation was found with other autoantibodies present in SLE. By contrast, a positive correlation was found between anti-M3 mAChR IgG and PGE2 serum levels in SLE. Conclusions: As anti-M3 mAChR antibodies present in the sera of SLE patients may be another factor in the pathogenesis of this disease, and the increment of PGE2 in the sera of SLE has a modulatory action on the inflammatory process, suggesting that the presence of these autoantibodies against M3 mAChR may contribute to sustained immune deregulation and the strong inflammatory component observed in SLE.

Serologic markers of autoimmunity in women with polycystic ovary syndrome

Abstract Study objective To evaluate serum levels of the common autoimmune markers, antinuclear antibodies (ANA), and anti-double-stranded DNA (dsDNA) in women with polycystic ovary syndrome (PCOS). Design A prospective case control study. Setting Ain Shams University Maternity Hospital. Materials and methods The included women were divided into 2 groups: group 1 included 50 women with PCOS according to Rotterdam Criteria (2003), and group 2 included 50 age-matched, healthy, fertile control women seeking contraception in the outpatient clinic. Transvaginal ultrasound was performed to evaluate the ovaries and uterus. Blood samples were obtained from all included women, who were in the follicular phase (days 3–7 of spontaneous menses or progestin-induced withdrawal bleeding) to determine serum levels of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and for serological tests namely ANA and anti-dsDNA. Main outcome measure Serum levels of ANA and dsDNA in women with PCOS. Results The mean serum levels of ANA were 9.0 ± 6.1 U/mL in group 1 versus 5.4 ± 2.3 U/mL, in group 2 ( p P 9.8 U/mL, with sensitivity and specificity of 77.8% and 100%, respectively. The positive and negative predictive values were 100% and 88.9%, respectively, with an overall accuracy of 0.944%. The best cut-off value of serum anti-dsDNA levels was >74 IU/mL, with sensitivity and specificity of 78.5% and 100.0%, respectively. The positive and negative predictive values were 100% and 92.3%, respectively, with an overall diagnostic accuracy of 0.878%. Major conclusions There is an association between PCOS and autoimmune markers such as ANA and anti-dsDNA which might affect the clinical management of those women.

Clinical characteristics and corticosteroid therapy in patients with autoimmune-hepatitis-induced liver failure.

To investigate the clinical features, response to corticosteroids, and prognosis of autoimmune hepatitis (AIH)-induced liver failure in China. A total of 22 patients (19 female and 3 male; average age 51 ± 15 years) with AIH-induced liver failure treated in our hospital from 2004 to 2012 were retrospectively analyzed. Clinical, biochemical and pathological characteristics of the 22 patients and responses to corticosteroid treatment in seven patients were examined retrospectively. The patients were divided into survivor and non-survivor groups, and the clinical characteristics and prognosis were compared between the two groups. The t test was used for data analysis of all categorical variables, and overall survival was calculated by the Kaplan-Meier method. At the time of diagnosis, mean IgG was 2473 ± 983 mg/dL, with three (18.8%) patients showing normal levels. All of the patients had elevated serum levels of antinuclear antibody (≥ 1:640). Liver histology from one patient showed diagnostic pathological changes, including massive necrosis and plasma cell infiltration. Four patients survived (18.2%) and 18 died (81.8%) without liver transplantation. The results showed that patients with low admission Model for End-Stage Liver Disease (MELD) scores (21.50 ± 2.08 vs 30.61 ± 6.70, P < 0.05) and corticosteroid therapy (100% vs 16.7%, P < 0.05) had better prognosis. A total of seven patients received corticosteroid therapy, of whom, four responded and survived, and the other three died. Survivors showed young age, shorter duration from diagnosis to corticosteroid therapy, low MELD score, and absence of hepatic encephalopathy at the time of corticosteroid administration. Six patients who were administered corticosteroids acquired fungal infections but recovered after antifungal therapy. Early diagnosis and corticosteroid therapy are essential for improving the prognosis of patients with AIH-induced liver failure without liver transplantation.