Antibody-negative Group Research Articles

Distribution characteristics of antinuclear antibodies in Guillain-Barré syndrome and its relationship with disease severity

BackgroundGuillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity. Materials and methodsWe retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups. ResultsIn this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group. ConclusionAnti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody negative patients. We observed statistical differences between antibody positive and negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

Clinical Observation of Serum Anti-PLA2R Antibody Levels in the Treatment of Idiopathic Membranous Nephropathy with Rituximab

Objective: To investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy with varying levels of serum phospholipase A2 receptor antibodies. Methods: A total of 137 patients with idiopathic membranous nephropathy admitted to Beijing Sixth Hospital were selected. Based on their blood PLA2R antibody levels before rituximab treatment, patients were categorized into the PLA2R antibody positive group (n = 94) and the PLA2R antibody negative group (n = 43). They were followed up for at least 1 year, during which the efficacy, measured through 24-hour urine protein quantification and serum albumin levels, were compared between the two groups before and after treatment. Results: After 3 months of treatment, there was no significant difference in the quantitative levels of 24-hour urine protein between the two groups (P > 0.05). However, after 6 and 12 months of treatment, there was a significant difference in the levels of 24-hour urine protein between the two groups (P < 0.05). Additionally, after 3 months of treatment, there was a notable difference in the serum albumin levels between the two groups (P < 0.05). However, after 6 and 12 months of treatment, there was no significant difference in serum albumin levels between the two groups (P > 0.05). Analysis of complications in the two groups revealed that in the positive group, 9 individuals experienced thrombosis, 5 had infections, and 11 developed acute kidney injury (AKI). In contrast, in the negative group, 5 individuals had thrombosis, 2 had infections, and 3 developed AKI. There was no statistically significant difference in complications between the two groups (P > 0.05). Conclusion: Serum anti-PLA2R antibody levels provide valuable insights into the clinical observation of rituximab treatment for idiopathic membranous nephropathy. They aid in understanding the disease’s pathogenesis, evaluating treatment efficacy, and predicting disease prognosis.

Characteristics and prognostic implications of peripheral blood lymphocyte subsets in patients with anti-MDA5 antibody positive dermatomyositis-interstitial lung disease

ObjectivesTo examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients.MethodsData were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5+ DM-ILD) and anti-MDA5 antibody negative group (MDA5− DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5+ DM-ILD.ResultsOut of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5+ and 194 were anti-MDA5−. Peripheral blood lymphocyte count, CD3+ count, percentage of CD3+, CD3+CD4+ count, and CD3+CD8+ count was lower in MDA5+ DM-ILD than in MDA5− DM-ILD− (all P < 0.001) as well as CD3−CD19+ count (P = 0.04). In MDA5+ DM-ILD, CD3+CD8+ count ≤ 49.22 cell/μL (HR = 3.81, 95%CI [1.20,12.14]) and CD3-CD19+ count ≤ 137.64 cell/μL (HR = 3.43, 95%CI [1.15,10.24]) were independent predictors of mortality. CD3+CD8+ count ≤ 31.38 cell/μL was associated with a higher mortality risk in all DM-ILD patients (HR = 8.6, 95%CI [2.12,31.44]) after adjusting for anti-MDA5 and other clinical characteristics.ConclusionSignificant lymphocytes decrease was observed in MDA5+ DM-ILD patients. CD3+CD8+ cell count was associated with worse prognosis in both MDA5+ DM-ILD and all DM-ILD patients.

Ophthalmologic Manifestations of Ocular Myasthenia Gravis

Purpose: We investigated the ophthalmic manifestations observed in patients diagnosed with ocular myasthenia gravis.Methods: In total, 58 patients diagnosed with ocular myasthenia gravis visited the ophthalmology and neurology departments between January 2011 and August 2022. Patients were followed for &gt; 6 months; their ophthalmic manifestations were analyzed retrospectively.Results: The study included 29 males and 29 females with a mean age of 55.52 ± 15.60 years. Among the patients, 31 tested positive for anti-acetylcholine receptor antibodies, resulting in a positive rate of 53.45%. Abnormalities in repeated nerve stimulation tests were observed in 33.33% of the patients. The antibody-positive group exhibited a higher frequency of progression to generalized myasthenia gravis (p = 0.011) and a higher incidence of chest abnormalities (p &lt; 0.001) compared to the antibody-negative group. Horizontal and vertical diplopia were commonly observed in a complex group of patients with diplopia and blepharoptosis (p &lt; 0.001); there was a difference in the pattern of strabismus between the diplopia single group with esotropia and the complex group with exotropia (p = 0.029). In addition, the combination group demonstrated a higher antibody titer (p = 0.034), a higher frequency of abnormalities in repeated nerve stimulation tests (p = 0.022), and a higher incidence of chest abnormalities (p = 0.022).Conclusions: The anti-acetylcholine receptor antibody-positive group had a higher incidence of progression to generalized myasthenia gravis; moreover, the complex group of patients with diplopia and ptosis exhibited elevated levels of anti-acetylcholine receptor antibodies and frequently accompanied both horizontal and vertical strabismus.

The effect of anti-phospholipid syndrome on pregnancy outcomes in patients with habitual abortus

Objective: The aim of this study was to research the pregnancy outcomes of women with anti-beta2 glycoprotein 1 and anti-cardiolipin antibody positivity and to determine the association with pregnancy morbidity.&#x0D; Materials and methods: This retrospective study contained pregnant women with anti-beta2 glycoprotein 1 and anti-cardiolipin antibody positivity and a control group without these antibodies. Totally 190 serum samples sent from Obstetrics and Gynecology clinics between January 2019 and January 2023 were analyzed in the medical microbiology laboratory of xx.&#x0D; Results: In a patient population separated into antibody-positive and antibody-negative groups, the gravida was found to be 3.8±0.1 and 3.5±0.3 respectively (p=0.333). Parity was 1.1±0.1 and 0.8±0.1 (p=0.071), abortion rates were 2.3±0.1 and 2.5±0.2 (p=0.659), and gestational age was 35.7±0.8 and 34±1.5 (p=0.047). Intrauterine fetal death was found to be higher in the antibody-positive group compared to the antibody-negative group (p=0.03). There was no noteworthy distinction noted between the two groups regarding additional pregnancy complications such as intrauterine growth restriction, oligohydramnios, gestational diabetes, and gestational hypertension (respectively p=0.623, 0.074, 0.312, 0.626). However, smoking was significantly higher in the antibody-positive group (p=0.049).&#x0D; Conclusion: Antiphospholipid syndrome adversely affects pregnancy outcomes. During the initial visit, a thorough patient history should be obtained, and in pregnant women with a history of poor obstetric outcomes or habitual abortions, this syndrome should be considered.

The impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney: A retrospective cohort study

IntroductionThe preoperative examination of kidney transplantation includes HLA antibody screening to initially determine the presence of preexisting donor-specific antibody (DSA) that mediates hyperacute rejection. Recipients with positive HLA antibodies require further HLA specificity analysis to type the antigen and determine the antigen mismatches between the donor and recipient. However, recipients with suspected antibodies would have no further HLA specificity analysis. It is unclear whether suspected HLA antibodies would affect renal graft function. This study aimed to explore the impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney and thus determine the necessity of routinely performing the HLA specificity analysis in recipients with suspected HLA antibodies preoperatively. MethodsThis is a single-center retrospective cohort study. 179 kidney transplant recipients (KTRs) were included and further divided into HLA antibody-negative group (Group 1) and HLA antibody-suspected groups (Group 2) based on the result of the pretransplant HLA antibody screen test. And the antibody-suspected group was further divided into a low-mismatched group (Group A) and a high-mismatched group (Group B) according to the HLA specificity analysis. We tracked the renal function indexes, biochemical indexes, and posttransplant adverse events within 5 years after transplantation and explored the necessity of further HLA specificity analysis in recipients with pretransplant suspected HLA antibodies. ResultsThere was no statistically significant difference in demographics between HLA antibody-negative group and HLA antibody-suspected groups. At 5 years of follow-up, the KTRs in HLA antibody-negative group had significantly higher eGFR levels, lower serum creatinine levels, and less urinary protein compared to those in antibody-suspected group. Meanwhile, the KTRs in low-mismatched group also had significantly higher eGFR levels, lower serum creatinine levels, and less proteinuria compared to those in high-mismatched group. Correlation analysis showed that the age of KTRs, urinary protein levels and the load capacity of HLA mismatches were associated with eGFR levels of KTRs at 5 year posttransplant. ConclusionKTRs with suspected HLA antibodies before kidney transplantation have worse graft function than the preoperative HLA antibody-negative recipients in the long-term posttransplant follow-up. The specific load capacity of HLA mismatches, the age of the recipient and the urinary protein was found to be negatively correlated with long-term posttransplant renal outcomes. It is necessary to undergo further HLA specificity analysis for recipients with suspected HLA antibodies in HLA antibody screen test to explicit HLA mismatches and improve long-term posttransplant outcomes.

Clinical and neuroelectrophysiological characteristics of primary peripheral nerve hyperexcitability syndrome

Objective: To investigate the clinical and neuroelectrophysiological characteristics of patients with primary peripheral nerve hyperexcitability syndrome (PNHS). Methods: The clinical data of 20 patients who were diagnosed with PNHS in Beijing Tiantan Hospital from April 2016 to January 2023 were retrospectively collected. All patients underwent neuroelectrophysiological examinations. Clinical and electrophysiological characteristics were compared between the antibody positive and antibody negative groups, according to serum and cerebrospinal fluid anti-contactin-associated protein-like 2 (CASPR2) and/or anti-leucine-rich glioma-inactivated protein 1 (LGI-1) antibodies. Results: There were 12 males and 8 females, with a mean age of (44.0±17.2) years and the disease course of [M (Q1, Q3)] 2.3 (1.1, 11.5) months. Motor symptoms included fasciculations, myokymia, muscle pain, cramps, and stiffness. These symptoms were commonly seen in the lower limbs (17 patients), followed by upper limbs (11 patients), face (11 patients) and trunk (9 patients). Nineteen (19/20) patients had sensory abnormalities and/or autonomic dysfunction, 13 patients had central nervous system involvement, and 5 patients had concomitant lung cancer or thymic lesions. The characteristic spontaneous potentials on needle electromyography (EMG) were myokymia potential (19 patients), fasciculation potential (12 patients), spastic potential (3 patients), neuromyotonic potential (1 patients), etc, which were commonly seen in the lower limb muscles, especially the gastrocnemius muscle(12 patients). After-discharge potential was found in 8 patients, and 7 were in the tibial nerve. Seven patients had positive serum anti-CASPR2 antibodies, and 3 of them had concomitant anti-LGI1 antibodies. And 1 patient had positive serum anti-LGI1 antibody alone. Compared with patients in the antibody negative group (n=12), the patients who had anti-VGKC complex antibodies (n=8) had a shorter course of disease [M (Q1, Q3): 1.8 (1, 2) months vs 9.5 (3.3, 20.3) months, P=0.012], higher incidence of after-discharge potential (6/8 vs 2/12, P=0.019). The immunotherapy regimen (multi-dru, single-drug, no immunotherapy: 6, 2, 0 patients) in antibody-positive patients was different from the antibody-negative group (3, 6, 3 patients, U=21.00, P=0.023). Conclusions: The symptoms of motor nerve hyperexcitation, characteristic EMG spontaneous potentials and after-discharge potentials in PNHS patients are most commonly seen in the lower limbs. Attention should be paid to concomitant sensory and autonomic nerve hyperexcitation. PNHS patients with positive serum anti-CASPR2 antibodies may require immunotherapy with multiple drugs.

Relationship between thyroid antibody levels and ovarian reserve function in infertile chinese women with normal thyroid-stimulating hormone

BackgroundTo analyze the relationship of thyroid peroxidase antibody and thyroid globulin antibody levels with ovarian reserve function in infertile women.MethodsThe data of 721 infertile patients who visited the hospital from January 2019 to September 2022 and whose thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels were in the normal range, were retrospectively analyzed. These patients were divided into two sets of three groups—the negative group, the 2.6 IU/ml ~ 100 IU/ml group and the TPOAb > 100 IU/ml group according to the TPOAb (thyroid peroxidase antibody) level, or the TgAb (anti-thyroglobulin antibody) negative group, the 14.58 IU/ml ~ 100 IU/ml group and the TgAb > 100 IU/ml group according to the TgAb level. They were compared for differences in ovarian reserve function index and thyroid hormone levels and analyzed for the relationship among thyroid antibody levels, ovarian reserve function, and thyroid hormone levels.ResultsWhen TSH > 2.5 mIU/L, the bFSH (basal follicle stimulating hormone) level in the TPOAb > 100 IU/ml group (9.10 ± 1.16 IU/L) was significantly higher than that in the TPOAb negative group (8.12 ± 1.97 IU/L) and the 2.6 IU/ml ~ 100 IU/ml group (7.90 ± 1.48 IU/L) (P < 0.05); when TSH ≤ 2.5 mIU/L, there were no statistically significant differences in the bFSH and AFC (antral follicle count) number at different TPOAb levels. Whether TSH ≤ 2.5 mIU/L or TSH > 2.5 mIU/L, there were no statistically significant differences in the bFSH and AFC number at different TgAb levels (P > 0.05). FT3/FT4 ratio in the TPOAb 2.6 IU/ml ~ 100 IU/ml group and the > 100 IU/ml group was significantly lower than in the negative group. FT3/FT4 ratio in the TgAb 14.58 ~ 100 IU/ml group and the > 100 IU/ml group was also significantly lower than in the TgAb negative group (P < 0.05). TSH level in the TPOAb > 100 IU/ml group was significantly higher than in the 2.6 ~ 100 IU/ml group and the TPOAb negative group, but there were no statistically significant differences among different TgAb groups.ConclusionsWhen TPOAb > 100 IU/ml and TSH > 2.5 mIU/L, it may affect the ovarian reserve function in infertile patients, and the mechanism may be associated with increased TSH and the imbalance of FT3/FT4 ratio caused by the increase of TPOAb.

Impact of thyroid autoimmunity on pregnancy outcomes in euthyroid women following fresh/frozen-thawed embryo transfer.

To investigate whether thyroid autoimmunity (TAI) is associated with assisted reproductive technology (ART) outcomes in euthyroid women undergoing fresh embryo transfer (ET) and frozen-thawed embryo transfer (FET). A retrospective cohort study. Pregnancy and neonatal outcome after freshETor FETwere compared between the positive and negative thyroid autoimmune antibody groups. A total of 5439 euthyroid women who started their ART cycle at our centre between 2015 and 2019 were included. The thyroid antibody positive group had a greater mean age than the thyroid antibody negative group (32(29,35) vs. 31(28,34), p < .001). Women with positive thyroid antibody presented with a higher prevalence of diminished ovarian reserve (DOR) (9.1% vs. 7.1%, p = .026) and lower number of oocyte retrieved (9(5,15) vs. 10(6,15), p = .020), but difference was not significant after adjusting for age. The pregnancy rate, live birth rate, pregnancy loss rate, preterm delivery rate and low birthweight rate between the thyroid antibody positive and thyroid antibody negative groups were comparable both in fresh ET cycles and FET cycles. Subanalysis of the treatment outcomes when using a stricter threshold of TSH of 2.5 mIU/L showed no difference to that achieved when using an upper limit of 4.78 mIU/L. The present study reveals that patients with anti-thyroid peroxidase antibodies (TPOAbs) and/or antithyroglobulin antibodies (TgAbs) showed no significant differences in pregnancy outcomes following fresh ET and FET when compared with patients with negative thyroid antibodies.

A Genetic Risk Score Distinguishes Different Types of Autoantibody-Mediated Membranous Nephropathy

Introduction: Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults and is characterized by detectable autoantibodies against glomerular antigens, most commonly phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain containing 7A (THSD7A). In Europeans, genetic variation in at least five loci, PLA2R1, HLA-DRB1, HLA-DQA1, IRF4, and NFKB1, affects the risk of disease. Here, we investigated the genetic risk differences between different autoantibody states. Methods: 1,409 MN individuals were genotyped genome-wide with a dense SNV array. The genetic risk score (GRS) was calculated utilizing the previously identified European MN loci, and results were compared with 4,929 healthy controls and 422 individuals with steroid-sensitive nephrotic syndrome. Results: GRS was calculated in the 759 MN individuals in whom antibody status was known. The GRS for MN was elevated in the anti-PLA2R1 antibody-positive (N = 372) compared with both the unaffected control (N = 4,929) and anti-THSD7A-positive (N = 31) groups (p < 0.0001 for both comparisons), suggesting that this GRS reflects anti-PLA2R1 MN. Among PLA2R1-positive patients, GRS was inversely correlated with age of disease onset (p = 0.009). Further, the GRS in the dual antibody-negative group (N = 355) was intermediate between controls and the PLA2R1-positive group (p < 0.0001). Conclusion: We demonstrate that the genetic risk factors for PLA2R1- and THSD7A-antibody-associated MN are different. A higher GRS is associated with younger age of onset of disease. Further, a proportion of antibody-negative MN cases have an elevated GRS similar to PLA2R1-positive disease. This suggests that in some individuals with negative serology the disease is driven by autoimmunity against PLA2R1.

Nasal immunization with AMH-INH-RFRP DNA vaccine for improving follicle development and fertility in buffaloes.

Inhibin DNA vaccine has already been proven to improve the fertility of animals. This study aimed to investigate the effects of a novel Anti-Müllerian hormone (AMH)-Inhibin (INH)-RF-amide-related peptides (RFRP) DNA vaccine on immune response and reproductive performance in buffalo. A total of 84 buffaloes were randomly divided into four groups and nasally immunized twice a day with 10 ml of either AMH-INH-RFRP DNA vaccines (3 × 1010 CFU/ml in group T1, 3 × 109 CFU/ml in group T2, and 3 × 108 CFU/ml in group T3) or PBS (as a control) for 3 days, respectively. All animals received a booster dose at an interval of 14 days. ELISA assay revealed that primary and booster immunization significantly increased the anti-AMH, anti-INH, and anti-RFRP antibody titers in the T2 group compared with that in the T3 group. After the primary immunization, the antibody positive rate was significantly higher in the T2 group than that in the T3 group. In addition, ELISA results indicated that concentrations of E2, IFN-γ, and IL-4 were significantly higher in the antibody-positive (P) group compared to the antibody-negative (N) group. In contrast, there was no significant difference in the concentrations of P4 between the P and N groups. Ultrasonography results revealed a highly significant increase of 2.02 mm in the diameter of ovulatory follicles in the P group compared to the N group. In parallel, growth speed of dominant follicles was significantly higher in the P group than that in the N group (1.33 ± 1.30 vs 1.13 ± 0.12). Furthermore, compared to N group, the rates of oestrus, ovulation, and conception were also significantly higher in the P group. The novel AMH-INH-RFRP DNA vaccine improves the proportion of oestrus, ovulation, and conception in buffalo by promoting the production of E2 and the growth of follicles.

Reliability of antibody tests for COVID-19 diagnosis

Objective: The reverse transcription–polymerase chain reaction test (RT-PCR) is the gold standard for the diagnosis of coronavirus&#x0D; disease 2019 (COVID-19), and antibody tests are useful as supplemental tools for diagnosis, for measuring the population’s immunity&#x0D; levels, and for checking infection in asymptomatic contacts. This study aimed to evaluate the reliability of five commercial antibody&#x0D; detection test kits.&#x0D; Materials and Methods: The reliability of the Colloidal Gold COVID-19 IgG/IgM Rapid Test Kit, Antibody Rapid Test Hotgen,&#x0D; Beijing Hotgen Biotech Co., Ltd., China), Abbott Chemiluminescent Microparticle Immunoassay (Illinois, USA), Roche&#x0D; Electrochemiluminescence Immunoassay (Roche Diagnostics, Switzerland), Siemens Chemiluminescence (Munich, Germany), and&#x0D; Euroimmun ELISA (Lübeck, Germany) for COVID-19 diagnosis was studied. The antibody-negative group included 50 sera from&#x0D; 2018, and the antibody-positive group included 98 patients with positive RT-PCR results from whom blood samples had been collected&#x0D; 3–9 weeks after hospital discharge. Statistical analysis was performed using SPSS version 23.0 (IBM Corporation, Armonk, NY, USA).&#x0D; The antibody tests’ validity and intra-assay reproducibility were examined, and the Cohen’s kappa coefficients were obtained. The&#x0D; disease prevalence was pegged at 10%.&#x0D; Results: The antibody tests’ sensitivity (69.12–72.46%) and positive predictive values (42.44–100.0%) were low, and their specificity&#x0D; (89.58–100%) and negative predictive values (96.31–97.03%) were high. Their accuracy rates varied from 87.54% to 97.25%, and their&#x0D; intra-assay coefficients of variation varied from 1% to 10%.&#x0D; Conclusion: The agreement between the results of the antibody detection test kits was higher when the kits were classified according to&#x0D; the targeted antigens. The time of blood sample collection, targeted antigens, and antibody types affected the results. Serological tests&#x0D; were found to be useful, and the commercial kits were found to be largely reliable, although, some parameters need to be improved.

Cancer associated autoantibodies in idiopathic inflammatory myopathies: A retrospective cohort from a single center in China

ObjectivesIdiopathic inflammatory myopathies (IIMs) are systemic, heterogeneous diseases, which mainly affect skeletal muscle. Myositis with cancer is often referred to as cancer-associated myositis (CAM), which is associated with poor prognosis. This study aimed to determine the cancer associated myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with IIMs. MethodsThis retrospective study enrolled 312 patients with IIMs who were treated at Tianjin Medical University General Hospital, China, from January 2015 to December 2020. Clinical data were collected. Serum MSAs, including anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ and anti-HMGCR antibodies were detected. Cancer-associated MSAs, their phenotypic and survival features were estimated through SPSS 20.0. ResultsThe results revealed that anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies with odds ratios (95% CI) of 8.70 (3.35–22.64) and 22.31 (4.32–115.05), respectively. Skin lesions, proximal weakness, dysphagia and dysarthria were observed more frequently in patients carrying anti-TIF1-γ antibody. By contrast, patients with anti-TIF1-γ antibody had a lower frequencies of fever, arthritis/arthralgia and interstitial lung disease (ILD). Anti-TIF1-γ antibody positive CAM comprised about half of CAM entities and had the characteristic of close temporal association with cancer detection/recurrence. Female-dominant, common reproductive system tumors were other clinical features of this subset. Besides, patients with anti-TIF1-γ antibody positive had significantly lower survival rates than the anti-TIF1-γ antibody negative group. ConclusionsAnti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies. Anti-TIF1-γ antibody positive CAM was a subset that comprised about half of CAM entities and had the characteristic of poor prognosis.

Clinical and prognostic features associated with anti-Ro52 autoantibodies in connective tissue diseases patients with interstitial lung disease.

To define the clinical and prognostic features associated with anti-Ro52 autoantibodies in patients with connective tissue diseases with interstitial lung disease (CTD-ILD). A total of 238 patients with CTD-ILD were included in this single-centre retrospective cohort study. Patients with positive anti-Ro52 antibodies were selected as the study group, and those with negative anti-Ro52 antibodies were included in the control group. Clinical and follow-up data were analysed. Among 238 patients, 145 (60.92%) were positive for the anti-Ro52 antibody. These patients were more likely to have respiratory symptoms at baseline, with more organising pneumonia (OP) patterns and worse forced vital capacity (FVC). Follow-up data were obtained for ILD progression in 170 patients. Varying degrees of progression in pulmonary function (PF) or imaging were found in 48 patients (28.24%) with CTD-ILD. A dichotomous logistic analysis based on the presence or absence of progress showed no correlation with anti-Ro52 antibodies. During the follow-up of 170 patients, there were 35 deaths: 24 in the anti-Ro52 antibody positive group and 11 in the anti-Ro52 antibody negative group. Kaplan-Meier survival curves were used to describe the difference in survival between the two groups (mortality 17.14% vs. 12.5%, log-rank p=0.287). The multivariate logistic analysis showed that ILD progression was associated with older age, worse FVC and diffusion capacity for carbon monoxide at baseline, higher levels of C-reactive protein, serum ferritin, immunoglobulin G and lower absolute lymphocyte count. Anti-Ro52 antibodies may predict more severe lung damage in CTD-ILD; however, anti-Ro52 antibodies were not correlated with progression and death in patients with ILD.

Characterization of immune checkpoint inhibitor-associated fulminant type 1 diabetes associated with autoantibody status and ethnic origin.

Fulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD). We enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin. Patients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days vs. 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD. IFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis

Anti-cyclic citrullinated peptide antibody testing is used to diagnose rheumatoid arthritis and associated with interstitial lung disease in RA. Herein, we investigate the relationship between anti-CCP antibody and ILD in SSc. We performed a retrospective analysis at a tertiary medical center between 2005 and 2019. Patients with SSc, systemic lupus erythematosus, and polymyositis/dermatomyositis (PM/DM) were evaluated for anti-CCP antibody and ILD. Additionally, medical records of SSc patients with ILD were reviewed. SSc patients had the highest anti-CCP antibody positivity rate compared to those with SLE and PM/DM. The incidence of ILD was higher in SSc patients with anti-CCP antibody than in those without. The usual interstitial pneumonia (UIP) incidence was higher in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. The DLCO was lower in the anti-CCP antibody-positive group than in the anti-CCP antibody-negative group. On multivariable analysis, factors associated with SSc-ILD were anti-CCP antibody or rheumatoid factor (β coefficient, 2.652 [95% CI 1.472 to 4.776]) and anti-Scl70 antibody (β coefficient, 4.011 [95% CI 2.142 to 7.508]). Anti-CCP antibody may be associated with a higher incidence of ILD in SSc. SSc patients with anti-CCP antibody may have more UIP pattern and lower DLCO.Trial Registration Retrospectively registered.

The association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome.

This study analyzed the association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome (pSS). A retrospective analysis was performed on patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital from January 1, 2010 to May 31, 2021, and who were diagnosed with pSS. Out of 191 patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria, 50 were positive for both anti-Ro/SSA and anti-La/SSB, whereas 97 had anti-Ro/SSA but not anti-La/SSB antibodies. Forty-four patients for whom neither anti-Ro/SSA nor anti-La/SSB antibodies were found were diagnosed with Sjögren's syndrome by minor salivary gland biopsy. The anti-Ro/SSA antibody-positive group showed higher rheumatoid factor (RF) levels than the anti-Ro/SSA antibody-negative group. The anti-La/SSB antibody-positive group showed lower unstimulated whole saliva (UWS), stimulated whole saliva (SWS), higher erythrocyte sedimentation rate and RF level than the anti-La/SSB antibody-negative group. In addition, the group with both anti-Ro/SSA and anti-La/SSB antibodies showed lower UWS than the group with only anti-Ro/SSA antibodies. However, there were no significant differences in UWS or SWS after taking pilocarpine, and C-reactive protein. UWS and SWS were lower when a patient was positive for anti-La/SSB, showing that anti-La/SSB is more likely to be involved in salivary gland hypofunction than anti-Ro/SSA in patients with pSS. Therefore, performing laboratory tests, including anti-La/SSB, helps predict the prognosis of salivary gland function in patients with suspected pSS.

Mucosal and Systemic Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination Determined by Severity of Primary Infection.

With much of the world infected with or vaccinated against severe acute respiratory syndrome coronavirus 2 (commonly abbreviated SARS-CoV-2; abbreviated here SARS2), understanding the immune responses to the SARS2 spike (S) protein in different situations is crucial to controlling the pandemic. We studied the clinical, systemic, mucosal, and cellular responses to two doses of SARS2 mRNA vaccines in 62 individuals with and without prior SARS2 infection that were divided into three groups based on antibody serostatus prior to vaccination and/or degree of disease symptoms among those with prior SARS2 infection: antibody negative (naive), low symptomatic, and symptomatic. Antibody negative were subjects who were antibody negative (i.e., those with no prior infection). Low symptomatic subjects were those who were antibody negative and had minimal or no symptoms at time of SARS2 infection. Symptomatic subjects were those who were antibody positive and symptomatic at time of SARS2 infection. All three groups were then studied when they received their SARS2 mRNA vaccines. In the previously SARS2-infected (based on antibody test) low symptomatic and symptomatic groups, reactogenic symptoms related to a recall response were elicited after the first vaccination. Anti-S trimer IgA and IgG titers, and neutralizing antibody titers, peaked after the 1st vaccination in the previously SARS2-infected groups and were significantly higher than for the SARS2 antibody-negative group in the plasma and nasal samples at most time points. Nasal and plasma IgA antibody responses were significantly higher in the low symptomatic group than in the symptomatic group at most time points. After the first vaccination, differences in cellular immunity were not evident between groups, but the activation-induced cell marker (AIM+) CD4+ cell response correlated with durability of IgG humoral immunity against the SARS2 S protein. In those SARS2-infected subjects, severity of infection dictated plasma and nasal IgA responses in primary infection as well as response to vaccination (peak responses and durability), which could have implications for continued protection against reinfection. Lingering differences between the SARS2-infected and SARS2-naive up to 10 months postvaccination could explain the decreased reinfection rates in the SARS2-infected vaccinees recently reported and suggests that additional strategies (such as boosting of the SARS2-naive vaccinees) are needed to narrow the differences observed between these groups. IMPORTANCE This study on SARS2 vaccination in those with and without previous exposure to the virus demonstrates that severity of infection dictates IgA responses in primary infection as well as response to vaccination (peak responses and durability), which could have implications for continued protection against reinfection.

The serum metabolomic profile of a distinct, inflammatory subtype of acute psychosis

A range of studies suggest that a proportion of psychosis may have an autoimmune basis, but this has not translated through into clinical practice—there is no biochemical test able to accurately identify psychosis resulting from an underlying inflammatory cause. Such a test would be an important step towards identifying who might require different treatments and have the potential to improve outcomes for patients. To identify novel subgroups within patients with acute psychosis we measured the serum nuclear magnetic resonance (NMR) metabolite profiles of 75 patients who had identified antibodies (anti-glycine receptor [GlyR], voltage-gated potassium channel [VGKC], Contactin-associated protein-like 2 [CASPR2], leucine-rich glioma inactivated 1 [LGI1], N-methyl-D-aspartate receptor [NMDAR] antibody) and 70 antibody negative patients matched for age, gender, and ethnicity. Clinical symptoms were assessed using the positive and negative syndrome scale (PANSS). Unsupervised principal component analysis identified two distinct biochemical signatures within the cohort. Orthogonal partial least squared discriminatory analysis revealed that the serum metabolomes of NMDAR, LGI1, and CASPR2 antibody psychosis patients were indistinct from the antibody negative control group while VGKC and GlyR antibody patients had significantly decreased lipoprotein fatty acids and increased amino acid concentrations. Furthermore, these patients had more severe presentation with higher PANSS scores than either the antibody negative controls or the NMDAR, LGI1, and CASPR2 antibody groups. These results suggest that a proportion of patients with acute psychosis have a distinct clinical and biochemical phenotype that may indicate an inflammatory subtype.