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1.
Arthritis Res Ther ; 26(1): 159, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261963

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) is the quintessential autoimmune disease, as it is characterized by hyperactivity of CD4+ T cells and subsequently drives lupus pathology. Follicular helper T (TFH) cells play an important role in B cell maturation and antibody production. However, which specific subset of cTFH cells drives B cell function and contributes to the development of anti-dsDNA antibodies and SLE pathogenesis remains unclear. METHODS: Peripheral blood mononuclear cells from SLE patients with inactive (n = 11) and active (n = 21) were used to determine and detect frequencies and phenotypes of circulating TFH cells (cTFH), memory cTFH, and B cell subsets. The correlations among cTFH cell subsets and phenotypes, B cell subsets, anti-dsDNA autoantibodies, and clinical parameters were analyzed. RESULTS: In subjects with active SLE, cTFH1 and cTFH17 cells were significantly expanded and activated. These expanded cTFH cells expressed memory phenotypes; cTFH1 cells were predominantly central memory (CM) type, while cTFH17 cells were largely effector memory (EM) type. Phenotyping B cell subsets in these patients showed increased frequencies of aNAV and DN2 B cells. Clinically, ICOS+ cTFH1, ICOS+ cTFH17 cells, and SLEDAI-2k scores were found to be correlated. Analysis of cTFH-B cell relationship revealed positive correlations among ICOS+ cTFH1 cells, aNAV B cells, and anti-dsDNA antibodies. Activation of ICOS+ cTFH17 cells was significantly related to the expansion of aNAV and DN2 B cells. The presence of CM cells in cTFH1 and cTFH17 subsets was correlated with aNAV and DN2 B cell frequencies. CONCLUSION: SLE cTFH cells were found to be polarized toward cTFH1 and cTFH17 cells; activation of these cTFH subsets was significantly associated with disease activity score, aNAV, DN2 B cell expansion, and anti-dsDNA antibody level. Thus, the interactions among cTFH1, cTFH17, and B cells likely contribute to the development of autoantibodies and the pathogenesis in SLE.


Subject(s)
Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/blood , Female , Adult , Male , Middle Aged , B-Lymphocytes/immunology , Lymphocyte Activation/immunology , T Follicular Helper Cells/immunology , Th17 Cells/immunology , Young Adult , Antibodies, Antinuclear/immunology , Antibodies, Antinuclear/blood
2.
JCI Insight ; 9(17)2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39253973

ABSTRACT

Elevated numbers of antibody-secreting cells (ASCs) and anti-double-stranded DNA (anti-dsDNA) antibodies are found in nasal polyp (NP) tissue. The presence of anti-dsDNA IgG in tissue prospectively predicts recurrent NP but the characteristics of the source ASCs are unknown. Here, we investigated whether NP B cells expressing the extrafollicular marker EBI2 have increased propensity for autoantibody production and evaluated the molecular characteristics of NP ASCs. NPs showed increased frequencies of anti-dsDNA IgG and total IgG ASCs compared with tonsils, with more pronounced differences among EBI2+ cells. In NPs, EBI2+ cells were frequently double negative (IgD-CD27-) and ASCs. Single-cell RNA-Seq analysis of tonsils and NPs revealed substantial differences in B lineage composition, including differences in percentages of ASCs, germinal centers, proliferative cells, and non-ASCs. NPs exhibited higher expression of specific isotypes (IGHE, IGHA1, IGHA2, and IGHG4) and mature plasma genes, including SDC1 and XBP1, than tonsils. Gene Ontology biological processes indicated upregulated NF-κB and downregulated apoptosis pathways in NP ASCs. Together, these data indicate that NP EBI2+ ASCs secret increased total and anti-dsDNA IgG compared with those from tonsils and had molecular features of mature plasma cell differentiation.


Subject(s)
Antibody-Producing Cells , Immunoglobulin G , Nasal Polyps , Humans , Nasal Polyps/immunology , Nasal Polyps/pathology , Nasal Polyps/metabolism , Antibody-Producing Cells/immunology , Antibody-Producing Cells/metabolism , Male , Female , Adult , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Middle Aged , Palatine Tonsil/immunology , Palatine Tonsil/cytology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Minor Histocompatibility Antigens/genetics , Minor Histocompatibility Antigens/metabolism , Minor Histocompatibility Antigens/immunology , Antibodies, Antinuclear/immunology , Aged , Young Adult
3.
Clin Lab ; 70(9)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39257108

ABSTRACT

BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of ˃ 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.


Subject(s)
Antibodies, Antinuclear , Antibodies, Monoclonal, Humanized , DNA , Humans , Female , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , DNA/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/blood , Middle Aged , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Immunosuppressive Agents/therapeutic use , Treatment Outcome , Autoantibodies/blood , Autoantibodies/immunology , Adult , Biomarkers/blood
4.
Front Immunol ; 15: 1390642, 2024.
Article in English | MEDLINE | ID: mdl-39221240

ABSTRACT

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies. Objectives: To evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data. Methods: A retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies - ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Smith) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher's exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant. Results: One-hundred and twenty-seven patients (n=127, mean age 53.43 ± 14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune hemolytic anemia and thrombocytopenia. Conclusions: In our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.


Subject(s)
Antibodies, Antinuclear , Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Female , Male , Adult , Retrospective Studies , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Middle Aged , Aged , Autoantibodies/blood , Autoantibodies/immunology , Young Adult
5.
BMC Immunol ; 25(1): 58, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39242985

ABSTRACT

BACKGROUND: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. RESULTS: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. CONCLUSION: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.


Subject(s)
Antibodies, Antinuclear , Lupus Erythematosus, Systemic , Magnesium , T-Lymphocytes, Regulatory , Animals , Lupus Erythematosus, Systemic/immunology , Female , Mice , Antibodies, Antinuclear/immunology , Antibodies, Antinuclear/blood , Magnesium/administration & dosage , T-Lymphocytes, Regulatory/immunology , Disease Models, Animal , Administration, Oral , Mice, Inbred MRL lpr , Autoantibodies/immunology , Autoantibodies/blood , Skin/pathology , Skin/immunology , Skin/drug effects , Skin Diseases/immunology , Skin Diseases/drug therapy , Skin Diseases/pathology
6.
BMJ Case Rep ; 17(8)2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39159977

ABSTRACT

Yellow nail syndrome (YNS) is a rare, acquired condition, characterised by at least two of the three clinical criteria: nail changes, respiratory tract disease and lymphoedema. Currently, the aetiology of YNS remains unknown; however, it is believed to be caused by impaired lymphatic drainage. Currently, there remain no definitive treatment options available and no prospective trials evaluating this. Management includes supportive care and symptomatic treatment. The presence of YNS has been described alongside various conditions, including autoimmune diseases, malignancies and drug exposures. To strengthen the literature on this topic, we present the case of a female patient with a history of anti-SSA and anti-SSB positive primary Sjögren's syndrome, who developed YNS in the immediate postpartum period.


Subject(s)
Sjogren's Syndrome , Yellow Nail Syndrome , Humans , Sjogren's Syndrome/complications , Sjogren's Syndrome/immunology , Sjogren's Syndrome/drug therapy , Sjogren's Syndrome/diagnosis , Female , Yellow Nail Syndrome/diagnosis , Adult , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology
7.
Front Immunol ; 15: 1410661, 2024.
Article in English | MEDLINE | ID: mdl-39091491

ABSTRACT

Objective: To clarify the impact of intravenous infusion of gamma globulin (IVIg) on antinuclear antibodies (ANAs) in children. Methods: A retrospective analysis was performed on the data of children with nonspecific autoantibody-related diseases whose antinuclear antibody (ANA) and autoantibody profiles were detected in our hospital from January to March 2022. A total of 108 patients with a clear history of IVIg infusion within 28 days composed the IVIg group, and 1201 patients without a history of IVIg infusion composed the non-IVIg group. Results: All patients in the IVIg group had either positive ANAs or positive autoantibodies. Anti-SSA, anti-Ro52 and anti-AMA Mi2 were the top three autoantibodies in the IVIg group. The proportions of patients who were positive for either of these three autoantibodies in the IVIg group were significantly greater than those in the non-IVIg group (all P<0.5). Spearman correlation analysis revealed that the signal intensities of anti-SSA and anti-Ro52 were negatively correlated with the number of days of ANA detection after IVIg infusion (P<0.05). Multiple logistic analyses revealed that a greater total dosage of IVIg, greater IVIg per kilogram of body weight, and fewer ANA detection days after IVIg infusion were independent risk factors for positive anti-SSA and anti-Ro52 results. Conclusions: It is recommended that if rheumatic diseases are suspected, ANA detection should be carried out beforeIVIg infusion. But for patients who are positive for at least one of these three autoantibodies after IVIg infusion, doctors should first consider adoptive antibodies.


Subject(s)
Antibodies, Antinuclear , Immunoglobulins, Intravenous , Humans , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Female , Male , Child , Retrospective Studies , Infusions, Intravenous , Child, Preschool , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/adverse effects , gamma-Globulins/immunology , gamma-Globulins/administration & dosage , Adolescent , Infant , Autoimmune Diseases/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/diagnosis
8.
Front Immunol ; 15: 1397103, 2024.
Article in English | MEDLINE | ID: mdl-39114649

ABSTRACT

Fetal autoimmune atrioventricular block (AVB) is a rare but potentially life-threatening condition. It results from the passage of maternal anti-SSA/Ro or Anti SSB/La auto-antibodies into the fetal circulation, leading to inflammation and fibrosis of the AV node and often to irreversible damage. Besides AVB, these antibodies can also cause cardiomyopathies, but there is no evidence linking them to tachyarrhythmias. We present the case of a patient with significant risk factors for fetal AVB: a prior history of hydrops fetalis, high anti-SSA/Ro antibody levels and hypothyroidism. In this case, the use of dexamethasone and intravenous immunoglobulin may have contributed to reversing the first-degree atrioventricular block detected at 19 weeks of gestation. Additionally, at 21 weeks, the fetus developed a tachyarrhythmia that needed treatment with flecainide. Soon after the birth, the newborn underwent ECG Holter and Wolff-Parkinson-White Syndrome (WPWS) was diagnosed. To our knowledge, the coexistence of fetal AVB and WPWS has never been described.


Subject(s)
Antibodies, Antinuclear , Atrioventricular Block , Tachycardia , Wolff-Parkinson-White Syndrome , Humans , Female , Pregnancy , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Wolff-Parkinson-White Syndrome/diagnosis , Wolff-Parkinson-White Syndrome/immunology , Tachycardia/diagnosis , Tachycardia/etiology , Atrioventricular Block/diagnosis , Atrioventricular Block/immunology , Atrioventricular Block/etiology , Adult , Infant, Newborn , Fetal Diseases/diagnosis , Fetal Diseases/immunology , Immunoglobulins, Intravenous/therapeutic use
10.
Arthritis Res Ther ; 26(1): 152, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39175076

ABSTRACT

BACKGROUND: Anti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs. METHODS: This retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth's logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories. RESULTS: This study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold. CONCLUSIONS: Among patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.


Subject(s)
Autoantibodies , Lung Diseases, Interstitial , Myositis , Humans , Lung Diseases, Interstitial/immunology , Myositis/immunology , Myositis/epidemiology , Myositis/complications , Male , Female , Middle Aged , Retrospective Studies , Autoantibodies/immunology , Autoantibodies/blood , Adult , Aged , Antibodies, Antinuclear/immunology , Antibodies, Antinuclear/blood , Ribonucleoproteins/immunology
11.
Clin Lab ; 70(8)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39193970

ABSTRACT

BACKGROUND: The examination of anti-double stranded DNA (ds-DNA) IgG antibody is of great significance for the diagnosis, differential diagnosis, assessment of disease activity, and prognosis of disease recurrence in SLE. METHODS: We used a chemiluminescence method to detect ds-DNA IgG and found that the levels of ds-DNA IgG antibody in the patient's serum were significantly increased and the indirect immunofluorescence (IIF) test result was negative. Laboratory tests show that the patient's RF level far exceeds the upper limit of their reference range. RESULTS: RF 110.6 IU/mL, ds-DNA IgG 753 IU/mL; After PEG6000 treatment, the RF was 108.7 IU/mL, and then the ds-DNA IgG was measured at 23.5 IU/mL. CONCLUSIONS: The RF IgM subtype is the main cause of RF interference in IgG antibody detection, mainly due to the binding of the Fc region of RF to the Fab segment of IgG. Combining with capture antibodies and labeled antibodies leads to the formation of non-specific detection signals, or directly reacting with the detected substance, resulting in false positive test results.


Subject(s)
Antibodies, Antinuclear , Immunoglobulin G , Rheumatoid Factor , Humans , Rheumatoid Factor/blood , Rheumatoid Factor/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/blood , Female , False Positive Reactions , DNA/immunology , Adult , Luminescent Measurements/methods , Male
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 835-839, 2024 Aug 15.
Article in Chinese | MEDLINE | ID: mdl-39148388

ABSTRACT

OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.


Subject(s)
Complement C1q , Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Complement C1q/immunology , Lupus Nephritis/immunology , Lupus Nephritis/blood , Female , Child , Male , Lupus Erythematosus, Systemic/immunology , Retrospective Studies , Adolescent , Autoantibodies/blood , Child, Preschool , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology
14.
PLoS One ; 19(8): e0307285, 2024.
Article in English | MEDLINE | ID: mdl-39163317

ABSTRACT

BACKGROUND/AIMS: Autoimmune hepatitis (AIH) is characterized by the presence of auto-antibodies and high blood immunoglobulin G (IgG) levels. In this study, the line immunoassay (LIA) was designed to assess various autoantibodies. METHODS: In total, 1371 patients who underwent autoimmune liver disease antibody testing between July 2019 and November 2022 were enrolled. Autoantibodies including antinuclear antibody (ANA) and anti-mitochondrial antibody (AMA) were tested, and clinical data were collected. Statistical analyses were performed by categorizing the data based on diagnosis and IgG quantification separately. A scoring system was applied to identify individuals with AIH. Patients were also classified into the AIH and non-AIH groups. RESULTS: The positivity rate for ANA was 80.2% in the AIH group. The IgG-high group had a high likelihood of the presence of detectable autoantibodies, with anti-Ro-52 being the most frequently detected antibody using LIA. The "Consider AIH" and "AMA" groups had 3-4 times more patients in the IgG-high group than in the "Not Considered" group. CONCLUSIONS: Among autoantibodies, the prevalence of ANA was the highest. As per LIA results, anti-Ro-52 was the most prevalent. AIH cannot be diagnosed based on IgG levels alone and must be distinguished via autoantibody testing. Therefore, extensive testing, including autoantibodies, IgG, ANA, and liver enzyme levels, will help accurately diagnose AIH.


Subject(s)
Antibodies, Antinuclear , Autoantibodies , Hepatitis, Autoimmune , Immunoglobulin G , Humans , Hepatitis, Autoimmune/immunology , Hepatitis, Autoimmune/blood , Hepatitis, Autoimmune/diagnosis , Male , Female , Middle Aged , Autoantibodies/blood , Autoantibodies/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Adult , Aged
15.
J Autoimmun ; 148: 103299, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39096716

ABSTRACT

OBJECTIVE: Autoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities. METHODS: Patients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses. RESULTS: 57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic. CONCLUSION: In this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic.


Subject(s)
Autoantibodies , Autoimmune Diseases , COVID-19 , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/epidemiology , Female , Male , SARS-CoV-2/immunology , Middle Aged , Autoimmune Diseases/immunology , Autoimmune Diseases/epidemiology , Autoimmune Diseases/diagnosis , Autoantibodies/immunology , Autoantibodies/blood , Aged , Adult , Connective Tissue Diseases/immunology , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/epidemiology , B-Lymphocytes/immunology , Autoimmunity , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Time Factors , Immunophenotyping
17.
Semin Arthritis Rheum ; 68: 152537, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39146916

ABSTRACT

OBJECTIVE: Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by diverse clinical manifestations yet lacking effective therapeutic strategies currently. This study aims to gain a thorough understanding of the clinical landscape of pSS and further delineate its clinical subtypes, thereby enabling the efficient management for pSS. METHODS: We conducted a cross-sectional observational study of 1318 pSS patients. The pSS patients were categorized and compared based on gender, anti-SSA antibodies, and labial salivary gland biopsies (LGSB). Unsupervised clustering analysis was employed to identify pSS subtypes using systemic involvement among patients. Furthermore, we assessed clinical and biological variances among these subtypes. RESULTS: Through group comparisons, we observed more pronounced extraglandular manifestations among male patients, SSA-negative group, and those with positive LGSB results. Based on systemic involvement, pSS patients were categorized into four groups. C1 exhibited minimal systemic involvement, lacking hematologic or serologic manifestations, with the lowest ESSDAI scores. C2 presented with serologic changes in all patients, partial joint involvement, and no hematologic systemic manifestations. C3 lacked joint involvement but all members displayed hematologic systemic involvement, with higher rates of renal, cutaneous, and systemic manifestations. C4 encompassed patients with joint and hematologic involvement, displaying the highest ESSDAI scores. The positivity rates of antibodies, immunological parameters, and inflammatory markers exhibited significant differences among the groups. Furthermore, notable variances were observed in the expression of peripheral blood transcriptomic modules among these groups. CONCLUSION: In this cohort study, we summarized the clinical characteristics of Chinese patients with pSS and identified four distinct subgroups of pSS based on systemic involvement, revealing clinical and molecular disparities that unveil distinct pathobiological endotypes. Our findings hold significant implications for clinical management.


Subject(s)
Sjogren's Syndrome , Humans , Sjogren's Syndrome/immunology , Sjogren's Syndrome/blood , Male , Female , Cross-Sectional Studies , Middle Aged , Adult , Aged , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Salivary Glands/pathology , Salivary Glands/immunology
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 605-611, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38948271

ABSTRACT

Objective: To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA). Methods: A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women. Result: A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-ß2 glycoprotein Ⅰ antibodies (ß2GPⅠ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both ß2GPⅠ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both ß2GPⅠ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies. Conclusion: Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.


Subject(s)
Abortion, Habitual , Autoantibodies , Immunity, Humoral , Maternal Age , Humans , Female , Adult , Abortion, Habitual/immunology , Retrospective Studies , Pregnancy , Autoantibodies/blood , Autoantibodies/immunology , Middle Aged , Antiphospholipid Syndrome/immunology , China , Lupus Erythematosus, Systemic/immunology , Sjogren's Syndrome/immunology , Young Adult , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Arthritis, Rheumatoid/immunology , Undifferentiated Connective Tissue Diseases/immunology , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Logistic Models
19.
Front Endocrinol (Lausanne) ; 15: 1403917, 2024.
Article in English | MEDLINE | ID: mdl-38948512

ABSTRACT

Objective: To identify the relationship between thyroid autoimmunity and antinuclear antibody (ANA) prevalence in Chinese pregnant women. Methods: The study involved 1923 first-trimester women who were measured for thyroid stimulating hormone (TSH) level, thyroid autoantibodies (thyroperoxidase antibody [TPOAb] and thyroglobulin antibody [TgAb]) and ANA titer. Social demographic data were collected through standardized questionnaires. Results: In this study, 23.3% of pregnant women tested positive for TPOAb and 9.9% tested positive for TgAb. Women with a positive ANA were more likely to be TPOAb-positive or TgAb-positive than women with a negative ANA (adjusted odds ratio [AOR] 1.96, 95% confidence interval [CI] 1.47-2.62 for TPOAb [+]; AOR 3.12, 95% CI 2.18-4.48 for TgAb[+]). In addition, ANA titers were closely associated with thyroid autoimmunity. Women with an ANA titer of >1:320 had a significant higher risk of being TPOAb positive or TgAb positive (AOR 4.49, 95% CI 1.48-13.66 for TPOAb [+]; AOR 5.51, 95% CI 1.65-18.49 for TgAb [+]). The higher the ANA titer, the greater the risk of developing thyroid autoimmunity, especially for those with a high ANA titer. Conclusions: ANA positivity is strongly correlated with thyroid autoimmunity. Further study is warranted to clarify the causal relationship between thyroid autoimmunity and ANA in pregnant women.This research is essential to evaluate and predict the risk of co-existing autoimmune disorders,leading to improved care for pregnancy and neonatal health.


Subject(s)
Antibodies, Antinuclear , Autoantibodies , Autoimmunity , Humans , Female , Pregnancy , Cross-Sectional Studies , Adult , China/epidemiology , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Prevalence , Autoantibodies/blood , Autoantibodies/immunology , Pregnancy Complications/immunology , Pregnancy Complications/epidemiology , Pregnancy Complications/blood , Young Adult , Thyroid Gland/immunology
20.
Autoimmunity ; 57(1): 2380465, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39034498

ABSTRACT

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.


Subject(s)
Antibodies, Antinuclear , BCG Vaccine , Disease Models, Animal , Lupus Erythematosus, Systemic , Animals , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/drug therapy , Mice , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , BCG Vaccine/immunology , Female , Cytokines/metabolism , Proteinuria/immunology , Proteinuria/etiology , Vaccination , Mice, Inbred MRL lpr , Mycobacterium bovis/immunology , Tumor Necrosis Factor-alpha/blood
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