Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice.

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 µg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.

The interference of anti-TSH autoantibody on clinical TSH detection.

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear. Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference. Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference. Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment.

Development and validation of a TAAbs and TAAs based non-invasive model for diagnosing lung cancer.

Background: Single Tumor-associated autoantibodies (TAAbs) and tumor-associated antigens (TAAs) have been found to have lower diagnostic efficacy in lung cancer. Our objective is to develop and validate a lung cancer prediction model that utilizes TAAbs and TAAs and to enhance the accuracy of lung cancer detection. Methods: 1830 subjects were randomly divided into training and validation sets at a 7:3 ratio for this study. Lasso regression analysis was used to remove collinear variables, whereas univariate logistic regression analysis was employed to identify potential independent risk factors for lung cancer. A diagnostic model was constructed using multivariate logistic analysis. The results were presented as a nomogram and assessed for various performance measures, including area under the curve, calibration curve, and decision curve analysis. Results: The diagnostic model was developed using gender, age, GAGE7, MAGE-A1, CA125, and CEA as variables. The training set had an AUC of 0.787, while the validation set had an AUC of 0.750. The calibration curves of the training and validation sets showed a strong agreement between anticipated and observed values. The nomogram performed better than any individual variable in both the training and validation sets in terms of net benefits for lung cancer detection, according to DCA analysis. Conclusions: This study proposes a diagnostic model for lung cancer that uses TAAbs and TAAs and incorporates individual characteristics. This model can be easily applied to personalized diagnosis.

Molecular typing of Kell, Kidd, and Duffy antigens in direct antiglobulin test-positive autoimmune hemolytic anemia patients.

BACKGROUND: In autoimmune hemolytic anemia (AIHA) patients, conventional pretransfusion testing is difficult to interpret due to the presence of autoantibodies which may show panreactivity. Molecular phenotyping of red cell antigens could potentially be used to precisely match blood units, thereby reducing the need to perform intensive serologic laboratory testing, hence time delay in providing transfusion to such patients. The aim of this study is to perform the molecular typing for Kell, Kidd, and Duffy blood group antigens in direct antiglobulin test (DAT)-positive red blood cells of AIHA patients and provide corresponding antigen-matched blood for transfusion therapy. MATERIALS AND METHODS: Blood samples from 50 normal blood donors and 30 DAT-positive AIHA patients were tested using standard serological techniques and polymerase chain reaction-based methods for Kell (K/k), Kidd (Jka/Jkb), and Duffy (Fya/Fyb) blood group systems. Five patients requiring blood transfusion were given donor blood units identical for Kell, Kidd, and Duffy antigens and followed up. RESULTS: Genotyping and phenotyping results were 100% concordant for normal blood donors. Serological phenotyping of minor red cell antigens showed varied degree of agglutination for AIHA patients. The molecular typing was able to detect the antigen frequency accurately in all samples. The results of genotyping were used to provide Kell-, Kidd-, and Duffy-matched blood for transfusion therapy to AIHA patients with no adverse reaction. CONCLUSION: Molecular blood group typing has proved immensely useful in the determination of actual antigen profile and hence in providing appropriate transfusion support in patients with AIHA reduced risk of transfusion reactions and alloimmunization.

Immune-mediated necrotizing myopathy: A comprehensive review of the pathogenesis, clinical features, and treatments.

Immune-mediated necrotizing myopathy (IMNM) is a rare and newly recognized autoimmune disease within the spectrum of idiopathic inflammatory myopathies. It is characterized by myositis-specific autoantibodies, elevated serum creatine kinase levels, inflammatory infiltrate, and weakness. IMNM can be classified into three subtypes based on the presence or absence of specific autoantibodies: anti-signal recognition particle myositis, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myositis, and seronegative IMNM. In recent years, IMNM has gained increasing attention and emerged as a research hotspot. Recent studies have suggested that the pathogenesis of IMNM is linked to aberrant activation of immune system, including immune responses mediated by antibodies, complement, and immune cells, particularly macrophages, as well as abnormal release of inflammatory factors. Non-immune mechanisms such as autophagy and endoplasmic reticulum stress also participate in this process. Additionally, genetic variations associated with IMNM have been identified, providing new insights into the genetic mechanisms of the disease. Progress has also been made in IMNM treatment research, including the use of immunosuppressants and the development of biologics. Despite the challenges in understanding the etiology and treatment of IMNM, the latest research findings offer important guidance and insights for delving deeper into the disease's pathogenic mechanisms and identifying new therapeutic strategies.

Immunological and therapeutic insights in autoimmune autonomic ganglionopathy: What is the position of apheresis in immunotherapy?

Autoimmune autonomic ganglionopathy (AAG) is characterized by various autonomic and extra-autonomic symptoms and is caused by autoantibodies against nicotinic acetylcholine receptors present in the autonomic ganglia (ganglionic acetylcholine receptor, gAChR), requiring immediate and aggressive intervention to prevent the exacerbation of symptoms. However, there is currently no internationally accepted standard of care for the immunotherapy of AAG, including apheresis. Although the rationale for the use of plasma exchange (PLEX) in AAG is strong, whereby pathogenic gAChR antibodies are removed, its overall impact on patient outcomes is not well-established. Based on previous case reports and small case series studies, we provide a comprehensive overview of the challenges and uncertainties surrounding the use of PLEX for the management of AAG and provide current practice recommendations to guide treatment decisions.

Automated immunoassay of serum NY-ESO-1 and XAGE1 antibodies for predicting clinical benefit with immune checkpoint inhibitor (ICI) in advanced non-small cell lung cancer.

BACKGROUND: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). METHODS: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). RESULTS: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39-0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32-0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13-0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098-0.75, p = 0.012) than the Ab-negatives (n = 11). CONCLUSION: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

Aberrant immunity in the oral cavity-a link with rheumatoid arthritis?

There are well established epidemiological links between rheumatoid arthritis and periodontitis. Recent data have started to shed light on the mechanisms that might underlie the relationship between these two complex diseases. Unravelling the roles of distinct pathways involved in these mechanisms has the potential to yield novel preventative and therapeutic strategies for both diseases. Perhaps most intriguingly, this represents an area where understanding the biology in the oral cavity might reveal fundamental advances in understanding immune regulation and the relationships between the host and microbiome. Here we seek to discuss aspects of the adaptive immune response that might link periodontitis and rheumatoid arthritis.

Macrophage activation and inflammatory priming by anti-MAA antibodies in rheumatoid arthritis.

We studied the effects of rheumatoid arthritis (RA) autoantibodies that target malondialdehyde-acetaldehyde protein adducts (anti-MAA) on inflammation and macrophage functions. We detected a profound reprogramming of gene expressions and the production of chemokines, such as CCL22 and CCL24, in anti-MAA exposed macrophages. Moreover, anti-MAA pretreatment promoted a more inflammatory cytokine profile upon TLR activation. Although anti-MAA are typically multi-reactive, we observed a prominent clonal diversity in inducing macrophage activation. Anti-MAA antibodies were not arthritogenic in mice, but altered a set of cytokine and growth factor encoding genes in the joints. In individuals at risk of RA anti-MAA IgG levels correlated with circulating inflammatory mediators prior to and at arthritis onset. Certain IgG anti-MAA clones may thus contribute to an inflammatory priming of the joint prior to the onset of systemic inflammation via inducing FcγR-mediated macrophage pre-activation and setting the stage for augmented responses to subsequent inflammatory stimuli.

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus.

Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b-/-) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b-/- mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.

Reg2 treatment is protective but the induced Reg2 autoantibody is destructive to the islets in NOD mice.

Regenerating family protein 2 (Reg2) is a trophic factor which stimulates ß-cell replication and resists islet destruction. However, Reg2 also serves as an islet autoantigen, which makes it complicated to judge the effectiveness in treating diabetes. How Reg2 treatment behaves in non-obese diabetic (NOD) mice is to be investigated. NOD mice were treated with recombinant Reg2 protein, Complete Freund's adjuvant (CFA) + PBS and CFA+Reg2 vaccinations, CFA+PBS- and CFA+Reg2-immunized antisera, and single chain variable fragment (scFv)-Reg2 and mIgG2a-Reg2 antibodies. Glycemic level, bodyweight, serum Reg2 antibody titer, glucose tolerance, and insulin secretion were determined. Islet morphological characteristics, insulitis, cell apoptosis, islet cell components, and T cell infiltration were analyzed by histological examinations. The autoantigenicity of constructed Reg2C and Reg2X fragments was determined in healthy BALB/c mice, and the bioactivity in stimulating cell proliferation and survival was assessed in insulinoma MIN6 cells. Reg2 administration alleviated diabetes in NOD mice with improved glucose tolerance and insulin secretion but elevated serum Reg2 autoantibodies. Histomorphometry showed reduced inflammatory area, TUNEL signal and CD8 + T cell infiltration, and increased ß-cell proportion in support of the islet-protective effect of Reg2 treatment. CFA+PBS and CFA+Reg2 immunizations prevented diabetic onset and alleviated insulitis while injections of the antisera offered mild protections. Antibody treatments accelerated diabetic onset without increasing the overall incidence. Reg2C fragment depletes antigenicity, but reserves protective activity in streptozotocin (STZ)-treated MIN6 cells. In conclusion, Reg2 treatment alleviates type 1 diabetes (T1D) by preserving islet ß-cells, but induces Reg2 autoantibody production which poses a potential risk of accelerating diabetic progression.

Anti-FHL1 autoantibodies in adult patients with myositis: a longitudinal follow-up analysis.

OBJECTIVES: To determine prevalence and clinical associations of anti-FHL1 autoantibodies in patients with idiopathic inflammatory myopathies (IIM), and to evaluate autoantibody levels over time. METHODS: Sera at the time of diagnosis from patients with IIM (n = 449), autoimmune disease controls (DC, n = 130), neuromuscular diseases (NMD, n = 16) and healthy controls (HC, n = 100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Patients with IIM FHL1+ and FHL1- were included in a longitudinal analysis. Serum levels were correlated to disease activity. RESULTS: Autoantibodies to FHL1 were more frequent in patients with IIM (122/449, 27%) compared with DC (Autoimmune DC and NMD, 13/146, 9%, p< 0.001) and HC (3/100,3%, p< 0.001). Anti-FHL1 levels were higher in IIM [median (IQR)=0.62 (0.15-1.04)] in comparison with DC [0.22 (0.08-0.58)], HC [0.35 (0.23-0.47)] and NMD [0.48 (0.36-0.80)] p< 0.001. Anti-FHL1+ patients with IIM were younger at time of diagnosis compared with the anti-FHL1- group (p= 0.05) and were seronegative for other autoantibodies in 25%.In the first follow-up anti-FHL1+ sample 20/33 (60%) positive at baseline had turned negative for anti-FHL1 autoantibodies. Anti-FHL1 autoantibodies rarely appeared after initiating treatment. Anti-FHL1 autoantibody levels correlated with CK (r = 0.62, p= 0.01), disease activity measure MYOACT (n = 14, p= 0.004) and inversely with manual muscle test-8 (r=-0.59, p= 0.02) at baseline. CONCLUSIONS: Anti-FHL1 autoantibodies were present in 27% of patients with IIM, of these 25% were negative for other autoantibodies. Other autoimmune diseases had lower frequencies and levels. Anti-FHL1 levels often decreased with immunosuppressive treatment, correlated with disease activity measures at diagnosis and rarely appeared after start of treatment.

Selenium levels and their association with thyroid autoimmunity and severe preeclampsia in pregnancy: Insights from a prospective ideal breast milk cohort study.

Objective: This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. Methods: 'Ideal Breast Milk (IBM) Cohort Study' included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 µg/L), suboptimal (70-99 µg/L), and optimal (≥ 100 µg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. Results: The median plasma selenium was 98.8 (range: 46.7-206.4) µg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Conclusion: Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

Coexistence of systemic sclerosis and cryopyrin-associated periodic syndrome.

Systemic sclerosis (SSc) and cryopyrin-associated periodic syndrome (CAPS) are distinct clinical entities belonging to the autoimmune and autoinflammatory diseases, respectively. The coexistence of the two entities has rarely been reported and is poorly characterized. Here, we described a case of a 38-year-old Japanese woman diagnosed with anti-centromere antibody-positive SSc and CAPS carrying the pathogenic mutation in the NLRP3 gene, with a detailed autoantibody profile by a high-throughput comprehensive protein array covering approximately 90% of the human transcriptome. The clinical manifestations of the patient were typical of both SSc and CAPS. Comprehensive autoantibody profiling identified 65 autoantibodies in the patient's serum and 78 autoantibodies in the serum of her daughter with CAPS, who carried the same NLRP3 mutation as the patient. SSc-associated autoantibodies (anti-DBT, anti- CENP-B, and anti-CENP-A) and anti-CD320 antibody were detected at high levels only in the patient's serum, while autoantibodies to the following four proteins were detected in the sera of both the patient and her daughter: TRIM21, LIMS1, CLIP4, and KAT2A. The TRRUST enrichment analysis identified NF-κB1 and RelA as overlapping key transcription factors that regulate the genes encoding proteins to which autoantibodies were detected in the patient and her daughter, therefore the autoantibody profile of the patient cannot be solely attributed to SSc, but may also be influenced by CAPS. Although autoimmune and autoinflammatory diseases are considered to be at opposite ends of the immunological spectrum, detailed autoantibody profiling may reveal a unique immunological landscape in an overlapping case of the two entities.

Low Levels of IgM Recognizing 4-Hydroxy-2-Nonenal-Modified Apolipoprotein A-I Peptide and Its Association with the Severity of Coronary Artery Disease in Taiwanese Patients.

Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251-262 and ApoA-I70-83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251-262 HNE, IgM anti-ApoA-I70-83 HNE, IgG anti-ApoA-I251-262, IgG anti-ApoA-I70-83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251-262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251-262 HNE may increase the severity of CAD at high and low levels, respectively.

Altered cytokine and chemokine profile linked to autoantibody and pathogen reactivity in mothers of autistic children.

Maternal autoimmunity, and more specifically, the production of specific maternal autoantibodies, has been associated with altered offspring neurodevelopment. Maternal autoantibody-related (MAR) autism is a subtype of autism that is linked to gestational exposure to certain combinations of autoantibodies to proteins known to be important for fetal neurodevelopment. We wanted to address whether mothers with autism-specific patterns of autoantibodies have a skewed cytokine and chemokine profile during an immune response to infection. To do so, we examined a subset of mothers from the Early Markers for Autism (EMA) study who either produced known patterns of MAR autoantibodies (MAR+) or did not (MAR-). We compared the cytokine/chemokine profiles of MAR+ and MAR- mothers in the context of positive immunoglobulin G (IgG) reactivity to several viral and parasitic agents. We observed that MAR+ mothers have a higher level of proinflammatory cytokine interferon-gamma regardless of IgG status. Additionally, when comparing MAR+ and MAR- mothers in the context of the different pathogens, MAR+ mothers consistently had increases in multiple proinflammatory cytokines and chemokines.

The Importance of Treating Subclinical Hypothyroidism in Patients With Immune Thrombocytopenia: A Case Report.

The leading cause of isolated thrombocytopenia in asymptomatic individuals is immune thrombocytopenia (ITP). It is an autoimmune disease characterized by decreased platelet counts caused by the immune system's destruction of platelets.  Sometimes, autoimmune thyroid diseases and ITP can coexist, which could cause an aggravated immune system response. When thyroid autoimmune diseases are present, treating ITP may become challenging. Treatment of the underlying thyroid disease in such individuals results in a significant improvement in platelet count, along with remission of the disease. It enhances the response to traditional ITP therapy. In this case report, we present a case of a 40-year-old female who was treated for ITP along with hypothyroidism, resulting in a considerable improvement in platelet count and a remission of the condition.

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.