Seropositive Group Research Articles

COVID-19 and Oncofertility: No SARS-CoV-2 in Semen but Inflammation Seems to Affect Sperm Parameters.

The COVID-19 pandemic, driven by SARS-CoV-2, led authorities to recommend halting assisted reproductive technology programs, focusing instead on fertility preservation, for cancer patients. The presence of SARS-CoV-2 in semen remains controversial. This multicentric prospective cohort study, conducted across 12 university medical centers, aimed to determine if SARS-CoV-2 is present in spermatozoa/seminal plasma in cancer patients by RT-PCR and to assess its impact on standard semen parameters. The levels of cytokines and TNF-α were measured in seminal fluid by ELISA. We enrolled 129 men who underwent sperm cryopreservation between July 7, 2020, and June 30, 2021. The 63 were included and tested for COVID-19 in nasal swab samples by RT-PCR and/or by serology. All patients were asymptomatic on the day of semen collection: 50 were uninfected, 8 had a positive nasal swab (PCR+) and 5 were seropositive. SARS-CoV-2 RNA was not detected in the seminal fluid or spermatozoa. Ejaculate volume was significantly lower in the PCR+ group compared to the uninfected group (median [IQR]: 2.6 mL [1.6-3.4] vs. 4.6 mL [2.6-5.2] p < 0.05). Total and progressive motility were lower in the PCR+ group compared to the seropositive group (32.5% [25.0-45.0] vs. 50% [49.0-55.0] p < 0.05, and 22.5% [10.0; 32.5] vs. 44.5% [40-49] p < 0.05). Higher TNF-α level was observed in the PCR+ group (1.9 pg/mL [0-3.9]) compared to the uninfected group (0 pg/mL [0-0.4]) p < 0.05. Although SARS-CoV-2 was not detected in the sperm samples of cancer patients who were PCR+, the infection appears to impact sperm parameters, likely due to inflammation.

Autoantibodies in type 1 diabetes: Prevalence and clinical profiles

Type 1 diabetes mellitus (T1D) is one of the most common chronic diseases in children and is associated with acute and serious chronic complications. T1D is characterized by the destruction of insulin-producing beta cells in the pancreas, with the emergence of circulating autoantibodies (a-Abs) targeting β cell antigens. Identifying autoantibodies can help predict the onset of T1D and associated autoimmune disorders, enhancing patient management strategies.We aimed to determine the prevalence of T1D autoantibodies and their clinical significance in the pediatric and adult populations. A multicenter cross-sectional study was carried out on 276 patient-first with T1D, including 167 pediatric (60.5 %) and 109 adult (39.5 %) cases, of which 144 were female and 132 were male (sex ratio= 0.91),with an average age of 14.1 ± 8.0 years. The immunological investigation was based on the detection of T1D related a-Abs, including anti-insulin, anti-glutamic acid decarboxylase (GAD65), anti-insulinoma-associated antigen 2 (IA2), and anti-zinc transporter 8 (ZnT8) specificities. The results revealed an overall autoantibody seropositivity rate of 75.36 % (n= 208). Among the positive cases, GAD65 antibodies were the most prevalent at 37.31 %, followed by anti-insulin and anti-ZnT8 antibodies, each at 36.59 %, and anti-IA2 at 28.62 %. Additionally, 45,67 % of patients had one a-Abs, 28.36 % had a two, 21.15 % had three, and 4.8 % had all four a-Abs.A statistically significant difference was observed between the seropositive and seronegative groups regarding the presence of associated autoimmune diseases (p = 0.005). These findings align with the existing literature, highlighting the importance and scientific value of detecting a-Abs in patients with T1D.

Are there differences in the clinical and laboratory features of patients with seronegative primary Sjögren's syndrome?

The objective of this study was to demonstrate the commonalities and distinctions between patients with seronegative and seropositive primary Sjögren's syndrome (pSS). The records of 399 patients with pSS seen between January 2010 and June 2023 were retrospectively examined. Patients with negative antiSSA/Ro, antiSSB/La, ANA, and RF antibodies comprised the seronegative group, while patients with at least one positive antibody were included in the seropositive group. The most common clinical features between the groups were arthralgia (81.2%), arthritis (11.5%), hematological involvement (19.8%), and pulmonary involvement (11.8%). In 41 patients (10.3%), no autoantibody positivity was detected. The number of patients with at least one extraarticular involvement was statistically more frequent in the seropositive group (p = 0.011). Dry mouth was found to be more prevalent among seronegative patients (p = 0.003). While hyperimmune gammaglobulinemia exhibited a higher prevalence within the seropositive group (p = 0.004), the occurrence of reduced complement levels was at similar rates in both groups. All deaths were observed exclusively within the seropositive group (17/358, 4.7%). No difference was observed between the two groups concerning mortality (p = 0.237) and malignancies (seropositive group: 9/358, 2.5% vs. seronegative group: 3/41, 7.3%, p = 0.115). There was a statistically significant association between low C4 levels (OR = 2.99 [1.09-8.16], p = 0.045 in model 1, OR = 3.10 [1.14-8.42], p = 0.022 in model 2), and the extraarticular findings. While hematological, renal, pulmonary, and neurological involvements are observed with similar frequency in both seronegative and seropositive pSS patients, the presence of extraarticular manifestations was more common in seropositive patients. Additionally, there was a relationship between extraarticular involvement and low C4 levels.

Cellular and humoral immunity and IgG subclass distribution after omicron XBB.1.5 monovalent vaccination in Japan

BackgroundUp to seven doses of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2) were administered to Japanese healthcare workers, until February 2024. The monovalent Omicron XBB.1.5 vaccine (hereafter called XBB.1.5 vaccine) was used for dose 7. ObjectiveAlthough the XBB.1.5 vaccine has been reported to induce a robust increase in neutralizing antibodies against the currently circulating Omicron variant BA.2.86, little is known about its serological effects in Japan, where the BNT162b2 mRNA vaccine is the most frequently administered in the world. Study designTwenty-five recipients of the XBB.1.5 vaccine, categorized as seronegative (n = 18) or seropositive (n = 7) based on their recent history of COVID-19, were analyzed. Neutralizing antibody titers against Omicron subvariants, receptor binding domain (RBD) IgG levels, IgG subclass distribution, and T-cell responses were assessed. ResultsWe found a significant increase in neutralizing antibody titers against XBB.1.5 and BA.2.86 variants following XBB.1.5 vaccination, particularly in seropositive individuals. No significant change in total RBD IgG levels was observed, indicating efficient induction of antibodies targeting regions outside the RBD by XBB.1.5 vaccination. IgG subclass analysis demonstrated no significant subclass switching after vaccination. T-cell responses against the virus were comparable between seropositive and seronegative groups. ConclusionsThe study suggests that XBB.1.5 vaccination enhances humoral immunity against Omicron variants without significant IgG subclass switching. However, some individuals with low pre-vaccination IgG titers did not exhibit increased antibody levels post-vaccination, raising concerns about potential immune tolerance.

The correlation between rituximab dose reduction and acute relapses of neuromyelitis optica spectrum disorder, lessons from COVID-19 epidemic

BackgroundCOVID-19 was a viral infection that led to a global pandemic in March 2020. At the beginning of the pandemic, clinicians encountered the challenge of how immunosuppressive treatments would affect the course of COVID-19 infection in people with autoimmune diseases. Neuromyelitis optica spectrum disorder is an autoimmune astrocytopathy that is caused by an inflammation in the CNS. Major treatments to prevent acute relapses include immunosuppressive drugs. Rituximab is a well-established immunosuppressive agent in NMOSD maintenance therapy. Some reports suggested that treatment with Rituximab might increase the risk of COVID-19 infection and its mortality in NMOSD. On the other hand, dose reduction or extended interval treatment might lead to acute relapses of NMOSD and permanent disability. MethodsIn this study, we evaluated the correlation between the dose of rituximab and the relapse rate of NMOSD during an epidemic. This was an observational study on 171 patients among whom 55 cases were seropositive. Some patients received full dose rituximab routinely (1000 mg/dose, every 6 months), but others were treated with half dose (500 mg/dose) during the epidemic. Also, some doses were prescribed with a delay, based on the level of CD19 and CD20. ResultsThe Pearson correlation coefficient (r) showed a negative and significant relation (r: - 0.19, p: 0.022) between the amount of drug and the number of relapses in the seropositive group, so low dosage of the drug was related to more acute relapses. In seronegative cases, there was not any valuable relationship. (p: 0.367). ConclusionLower dose of rituximab, especially in seropositive NMOSD patients, can potentially lead to acute relapses. So, the more frequent evaluation of the CD19, CD20, and, CD27 levels, and the general clinical condition of the patients should be considered.

Ocular effects of synthetic cannabinoids: a case-control study.

To evaluate the ocular effects of "Bonzai", a synthetic cannabinoid (SC), in seropositive and seronegative users. Sixty eyes of 60 consecutive male patients with a history of "Bonzai" use and 30 eyes of 30 age-matched male healthy controls were enrolled in this case-control study. Patients with past "Bonzai" use were grouped as seropositive (n:30) and seronegative (n:30) according to urine toxicology tests. All groups were compared for blood pressures, intraocular pressure, foveal and parafoveal retinal thicknesses, subfoveal and parafoveal choroidal thicknesses, measurements of the peripapillary retinal nerve fibre layer (RNFL), and macular ganglion cell complex (GCC), subfoveal total choroidal, luminal and stromal areas, and choroidal vascularity index (CVI). No differences were noted in blood pressures between the groups (p > 0.05). The mean intraocular pressure was significantly lower in the seropositive group than in the other groups (p < 0.001). Foveal and retinal thicknesses, RNFL, and GCC measurements did not differ between the groups (p > 0.05). Subfoveal and parafoveal choroidal thicknesses and areas were lower in the seropositive group than in the other groups (p < 0.001, for all). CVI increased in both groups with "Bonzai" use compared to the control group (p < 0.001, for all). This study indicates that intraocular pressure may decrease, and choroidal changes may be observed in SC users. Further clinical studies with a larger sample size, especially using purified SC for therapeutic purposes, are needed to confirm the present findings, and further histopathologic studies are required to clarify the changes in the choroid despite SC seronegativity. NCT06235346.

Analysis of clinical features and outcomes in patients with ocular myasthenia gravis according to anti-acetylcholine receptor antibody-seropositivity.

To comparatively analyze the clinical characteristics of patients with ocular myasthenia gravis (OMG) referred to an ophthalmology clinic, according to anti-acetylcholine receptor antibody (AchR Ab)-seropositivity. Retrospective Cohort Study. Medical records of patients with OMG who presented to a tertiary eye care center between 2003 and 2020 were retrospectively reviewed. Demographics, ophthalmologic characteristics, response to medical treatment, presence of autoimmune thyroid disease and thyroid autoantibody were compared between the AchR Ab seropositive and seronegative groups. A total of 130 patients with OMG were identified; among them, 46 patients (35.4%) had autoantibody against acetylcholine receptors. The mean age at symptom onset was 42.4 ± 18.9 years. There were no differences in mean age at symptom onset, gender ratio, and mean follow-up period between patients with seropositive and seronegative OMG. Graves ophthalmopathy was significantly more frequent in seronegative patients (p = 0.04), while thymic disease (p < 0.01) was more frequent in seropositive patients (p < 0.01). Among patients with seropositive OMG, 52.3% showed a good response to medical treatment, while only 31.4% of the seronegative patients were classified as good responders (p = 0.01). Thyroid dysfunction was found in 27.4% patients with OMG and the proportion of thyroid dysfunction was not different according to anti-acetylcholine receptor antibody-seropositivity. Seropositivity to acetylcholine receptor antibody is associated with a better response to medical treatment and lower risk of concomitant autoimmune thyroid disease in patients with OMG.

Epstein-Barr Virus and Cytomegalovirus Coinfection in Egyptian COVID-19 Patients

Abstract Background Reactivation of herpesviruses such as Epstein–Barr virus (EBV) and cytomegalovirus (CMV) in COVID-19 patients reported in many studies in different countries during the pandemic. We aimed to measure prevalence of this coinfection in Egyptian COVID-19 patients with elevated liver enzymes and its relation to the severity and the outcome of COVID-19 infection in those patients. Methods A cross-sectional study was carried out on 110 COVID-19 patients with elevated liver enzymes regardless the severity of COVID-19 disease. All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest). Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) were determined by VCA IgM and CMV IgM respectively by enzyme linked immunosorbent assay (Elisa). Results Of the included 110 patients with COVID-19 illness, 5 (4.5%) were Epstein-Barr virus seropositive and 5 (4.5%) were Human cytomegalovirus seropositive. Regarding the symptoms, the incidence of fever in the EBV &amp; CMV seropositive group was apparently higher than that in the EBV &amp; CMV seronegative group. In lab tests, the platelets and albumin of EBV &amp; CMV seropositive group decreased more significantly than EBV &amp; HCMV seronegative group, and serum ferritin, D-dimer and c-reactive protein show higher values in seropositive group than in seronegative group but not statistically significant. Seropositive group had received higher doses of steroids than seronegative group. The median of hospital stay in seropositive group was (15 days) nearly double that of seronegative group with statistically significant difference between both groups. Conclusion Coinfection of EBV and CMV in COVID-19 Egyptian has no effect on the disease severity or the clinical outcome of the disease. But Those patients had higher hospital stay duration.

Pretransplantation assessment of BK virus seropositivity in kidney donors and recipients

Background: BK virus (BKV) is a member of the polyomavirus family. The determination of anti-BKV immunoglobulin G (IgG) antibody levels in kidney donors and recipients has been reported as a possible predictor of the risk of BK nephropathy. Allograft dysfunction is a significant risk factor. The main objective of this study was to address the high prevalence of renal failure due to BKV nephropathy in kidney transplant recipients. This investigation aims to determine whether donors and recipients of renal transplants had BKV IgG antibodies before transplantation. Methods: Blood samples were collected from 46 kidney transplant recipients and their corresponding 46 donors. An enzyme-linked immunosorbent assay was used to qualitatively analyze human BKV IgG. Results: Ninety-two participants, 46 kidney transplant donors, and 46 kidney transplant recipients, were analyzed. Pretransplantation anti-BKV antibody levels were higher in kidney transplant donors (73%) than in recipients (63%). Donors and recipients included in the study were grouped into seropositive and seronegative recipients, with the highest proportion of seropositive recipient-donor groups (48%) and the lowest percentages in the seronegative donor and seronegative recipient groups. Fifty-one percent of the participants were male and 49% were female. The age distribution of most subjects was &gt;50 years old. Conclusion: BKV can cause kidney transplant rejection. Routine screening of transplant recipients and donors for BKV IgG seropositivity is recommended before renal transplantation. This can improve transplant outcomes and prevent rejection.

Tixagevimab/Cilgavimab for COVID-19 Pre-Exposure Prophylaxis in Hematologic Patients-A Tailored Approach Based on SARS-CoV-2 Vaccine Response.

Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host's immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, p < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, p < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, p < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), p = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints.

Post-vaccine immune status surveillance of Covishield vaccine and associated AEFI in previously SARS-Cov-2 infected seropositive and seronegative population in Assam.

COVID-19 an infectious disease caused by the SARS-CoV-2 virus, started in late 2019 and became a pandemic within a short period. To respond to the pandemic vaccines like Covishield, Covaxin, Sputnik V, Covovax, etc., were developed rapidly. However, there were raising concerns about the development of immunity as well as adverse events following vaccination. To compare anti-SARS-CoV-2 IgG antibody titres at different time-points post-vaccination between baseline seropositive and seronegative groups and to assess the adverse events following the 1st dose of Covishield vaccine among adult beneficiaries attending vaccination centre in a tertiary care hospital of Upper Assam. Prospective Cohort study was conducted from July 2021 to June 2022 among adult beneficiaries receiving the Covishield vaccine. The oral questionnaire was used incorporating socio-demographic variables, and clinical profiles including co-morbidities and adverse events following vaccination. Data analysis was done by Microsoft Excel and SPSS. Out of a total of 146 study participants, IgG estimation showed 61% as seropositive and the rest as seronegative. A total of 55.40% had minor adverse events, majority of them were females (53.08%) and 88.80% belonged to 18-59 years compared to 11.11% above 60 years of age. The majority (71.60%) did not have any co-morbidities and the major AEFI was NIL among the study participants. The study group had 61% seropositive previously infected. Covishield vaccination induces an immune response and 90% seroconversion is achieved after 1st dose (booster dose). Antibody titres of the seropositive group by natural infection of SARS-CoV-2 were higher than seronegative cohort seroconverted by vaccination. The AEFI observed were minor and can be commented as safer.

Pediatric Autoimmune Encephalitis: A Nationwide Study in Latvia.

Autoimmune encephalitis (AE) is the third most common encephalitis in children. Diagnosis can be challenging due to overlapping and diverse clinical presentations as well as various investigation results. This study aims to characterize the clinical, diagnostic features, as well as treatment and outcomes of AE in children and determine the incidence of pediatric AE in Latvia. The study was conducted at the Children's Clinical University Hospital in Riga. The study participants were patients under the age of 18 years diagnosed with AE from 2014 to 2022. Data regarding clinical characteristics, investigation findings, treatment strategy, and outcomes were retrospectively collected from the medical history data system. We included 18 pediatric patients diagnosed with AE. The mean incidence of pediatric AE in Latvia was 0.56 per 100,000 children. Most patients (66.6%) had seronegative AE. In the seropositive group, the most common was anti-methyl-D-aspartate receptor AE, with two patients having other antibodies. The most prevalent clinical features were personality change, cognitive impairment, autonomic dysfunction, and movement disorders. The majority of patients (58.8%) received first-line treatment only. More than half (55.6%) of our AE patient group had long-term sequelae. Our study shows that the pediatric AE incidence in Latvia is similar to what has been previously reported in other studies. A relatively high proportion of seronegative AE was present in our cohort, indicating that awareness of possible misdiagnosis should be raised. Further research is needed to better understand the underlying mechanisms, characterize clinical features, and determine the treatment of choice in different situations to improve long-term outcomes.

Early predictive factors in routine clinical practice for rituximab therapy response in patients with rheumatoid arthritis.

Identifying early predictive factors of how rheumatoid arthritis (RA) patients respond to rituximab (RTX) treatment is crucial for both individual treatment outcome and the improvement of clinical practice overall. This study aimed to identify early predictive factors available in standard clinical practice for predicting RTX treatment outcomes in RA patients. Data on seventy patients diagnosed with RA treated with RTX (two 1,000 mg doses 2 weeks apart or two 500 mg doses 2 weeks apart) were retrospectively collected. Baseline information collected at the initiation of RTX treatment included patient characteristics such as age, sex, disease duration, disease activity, Health Assessment Questionnaire score, erythrocyte sedimentation rate, C-reactive protein, and serological status regarding rheumatoid factor (RF) and anti-cyclic citrullinated protein antibodies (ACPA). Clinical responses were analyzed 6 months after RTX initiation using the European Alliance of Associations for Rheumatology criteria. Potential predictors associated with positive RTX response at 6 months were identified using a multivariate ordinal logistic regression model. The analysis showed that persistently active RA disease, Disease Activity Score with 28-joint count (DAS28) values at the treatment onset and after 3 months, along with erythrocyte sedimentation rate at treatment initiation, were negatively correlated with the response to RTX therapy (p < 0.05). All these correlations were statistically significant at the 99% confidence interval. The correlation and logistic regression analyses indicate that there are no significant association between RF and ACPA concerning therapy response, despite a higher number of RTX responders in the seropositive groups. Additionally, the study emphasizes the prognostic significance of the DAS28 value at treatment initiation in predicting therapy response at 6 months. The optimal model for predicting RTX response at 6 months involves the interaction of all clinical factors examined in this study, as revealed by the analysis of multiple variables.

Anti-Ro and anti-La seropositivity is associated with increased rates of ischemic heart disease in adults: Results from a large population-based study

Background and aimsEmerging evidence suggests an arrhythmogenic effect of Anti-Ro/SSA (anti-Ro) and anti-La/SSB (anti-La) antibodies in adults, potentially involving a subclinical intracardiac inflammatory process. Despite the established association between inflammation and ischemic heart disease (IHD), it is noteworthy that as of now no study has delved into the potential link between these antibodies and IHD. This population-based study aimed to examine the association between anti-Ro/La seropositivity and IHD in the general adult population. MethodsWe conducted a retrospective study using electronic medical records from the largest health maintenance organization in Israel. Patients with positive serology for either or both anti-Ro and anti-La antibodies were included, along with matched controls. Multivariate logistic regression models were utilized to assess the odds of IHD in seropositive patients compared to controls. ResultsAmong 17,231 seropositive patients and 84,368 controls, the rate of IHD was significantly higher in the seropositive group (9.7 % vs. 8.1 %,OR = 1.23; 95%CI 1.14–1.31; p<0.001). The association was more pronounced in younger patients [<40 years old (OR = 3.36; 95%CI 1.66–6.82; p<0.001), 40–49 years old (OR = 1.85; 95%CI 1.26–2.73; p<0.01), 50–59 years old (OR = 1.87; 95%CI 1.55–2.26; p<0.001), 60–69 years old (OR = 1.26; 95%CI 1.11–1.42; p<0.001), ≥70 years old (OR = 1.11; 95%CI 1.03–1.20; p<0.01)], as well as in patients with fewer traditional cardiovascular risk-factors (none:OR = 1.29; 95 % CI 1.09 to 1.77; p<0.01, 1–2:OR = 1.30; 95 % CI 1.19 to 1.41; p<0.001, ≥3:OR = 1.09; 95 % CI 0.99 to 1.21; p=0.076). ConclusionsOur study demonstrates for the first time a positive association between anti-Ro/La seropositivity and IHD in the general adult population, especially among younger individuals with fewer traditional cardiovascular risk factors.

The Relationship between Seropositive Rheumatoid Arthritis and Congestive Heart Failure: A Nationwide Longitudinal Cohort Study in Korea.

Objectives: The aim of this nationwide longitudinal cohort study is to determine the risk of congestive heart failure (CHF) associated with a seropositive rheumatoid arthritis (RA) population in Korea. Methods: In this study, National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data from 2002 to 2003 were used. The cohort was followed up with for 12 years until December of 2015. Seropositive RA was defined as a patient prescribed with a disease-modifying anti-rheumatic drug (DMARD) among patients with the International Classification of Diseases code M05 (seropositive RA). Patients who were diagnosed before 2004 were excluded. The seropositive RA group consisted of 2765 patients, and a total of 13,825 patients were in the control group. The Kaplan-Meier method was used to calculate the 12-year CHF incidence rate for each group. A Cox proportional hazards regression analysis was used to estimate the hazard ratio of CHF. Results: The hazard ratio of CHF in the seropositive RA group was 2.41 (95% confidence interval (CI): 1.40-4.14) after adjusting for age and sex. The adjusted hazard ratio of CHF in the seropositive RA group was 2.50 (95% CI: 1.45-4.30) after adjusting for age, sex, income, and comorbidities. In females aged ≥65 and aged <65, the incidence rates in the non-hypertension, non-diabetes mellitus, and non-dyslipidemia subgroups were significantly higher in the seropositive RA group than in the control group. Conclusions: This nationwide longitudinal cohort study shows an increased risk of CHF in patients with seropositive RA.

Comparing FGFR-3 and TS-HDS Seropositive Small Fiber Neuropathy: Unique Patient Features, Symptoms, Laboratory, and Nerve Conduction Study Findings.

Small fiber neuropathy presents a significant diagnostic and therapeutic challenge. To solve this challenge, efforts have been made to identify autoantibodies associated with this condition. Previous literature has often considered tri-sulfated heparin disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR3) as a singular seropositive group and/or focused primarily on symptomatic associations. One hundred seventy-two small fiber neuropathy patients with a Washington University Sensory Neuropathy panel were selected for TS-HDS seropositivity, FGFR-3 seropositivity, and seronegative controls. Data were collected to on the demographic, symptomatic, and laboratory profiles of each subgroup. Percent female (P = 0.0043), frequency of neuropathic pain symptoms (P = 0.0074), and erythrocyte sedimentation rate (P = 0.0293), vitamin D (P < 0.0001), and vitamin B12 (P = 0.0033) differed between the groups. Skin biopsy was more frequently normal within both the FGFR-3 and the TS-HDS cohort (P = 0.0253). TS-HDS and FGFR-3 display a distinct phenotype from both controls and one another. Immunoglobulin M (IgM) against FGFR-3 and IgM against TS-HDS may be individually valuable markers for the development of distinct clinical phenotypes.

#2291 ANCA negative vasculitis—the unmet need within small vessel vasculitis

Abstract Background and Aims ANCA negative small vessel vasculitis with renal involvement has been described in a number of cohorts. Though comprehensive studies comparing these individuals to ANCA positive patients are lacking and they are routinely excluded from clinical trials. Whilst the numbers are smaller than those with ANCA positivity, they still make up a large proportion of small vessel vasculitidies (Fig. 1). The absence of detectable circulating ANCA is thought to indicate a distinct spectrum of the disease. There remains unanswered questions regarding the pathophysiology, diagnosis and management of patients with seronegative AAGN. We present data from Croatian referral center. Method Study included 106 AAV patients with biopsy proven renal involvement in the period from 2007-2017. Category variables were analysed with Fisher Exact test and continuous with Kruskal-Wallis test. Statistical difference was then analysed post hoc with Chi-square test. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between clinical phenotypes and finding significant predictors regarding outcomes which were defined as combined outcome end-stage renal disease and death (ESRDD), ESRD alone, the death outcome alone and relapse rate. Results 106 AAV patients with renal involvement were included: 66 (61.1%) MPA, 20 (18.5%) GPA, 20 (18.5%) RLV. 14 (13%) were PR3-ANCA positive, 57 (52.8%) MPO ANCA positive, 5 (4.6%) PR3-ANCA+MPO-ANCA and 32 (29.6%) ANCA negative patients. ANCA negative patients were comparatively younger (p = 0.02) and presented with more renal limited vasculitis (RLV; p &amp;lt; 0.001), lower BVAS (p = 0.003) and lower CRP (p = 0.001). ANCA negative patients usually presented with nephrotic syndrome compared to positive ones which presented with rapid progressive nephritic syndrome or acute nephritic syndrome (p = 0.027). 24-hour proteinuria levels were higher in ANCA negative group (p = 0.003). Though statistical difference was not reached, there was tendency for ANCA negatives to receive less plasmapheresis (p = 0.074). Histologically there were no differences between ANCA positive and ANCA-negative patients. On sub analysis ANCA negatives versus individual seropositive groups, there was tendency that ANCA negatives and MPO-ANCA patients had lower percentage of glomerular crescents (p = 0.092) but more acute tubular damage (p = 0.087). There were no differences in clinical outcomes between the groups. Conclusion ANCA negative vasculitis form a large proportion of small vessel vasculitidies and present with different clinical laboratory and histological (renal) characteristics than ANCA positive ones. More often than not disease seems to be renal limited and patients tend to be younger. Due to the rarity of the disease, there remains unanswered questions regarding the pathophysiology, diagnosis and management of these patients. This study highlights noteworthy distinctions between the two groups. Whether these differences warrant adjustments in treatment algorithms or a reconsideration of the classification of small vessel vasculitis remains to be determined. Further investigation into the pathogenetic mechanisms of seronegative AAVs is essential.

The first involved joints and associated factors in patients with rheumatoid arthritis.

This study aimed to investigate the first involved joints and associated factors in Turkish patients with rheumatoid arthritis (RA). This retrospective cross-sectional study included 300 newly diagnosed and disease-modifying antirheumatic drug-naïve RA patients (240 females, 60 males; mean age: 54±1.2 years; range, 18 to 82 years). Baseline demographic, clinical, and laboratory data were evaluated between January 2022 and December 2022. The patients were divided into four groups according to autoantibody profile: antibody-negative patients (Group 1; both RF and anti-CCP were negative in this group of patients), RF-positive patients (Group 2), anti-CCP-positive patients (Group 3), and patients with dual seropositivity with RF and antiCCP (Group 4). The patients were also divided into two groups according to the size of the first affected joint: patients with SJI at diagnosis and patients without SJI involvement at diagnosis. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody positivity rates were 40.3% and 35.6%, respectively. The mean lag time to diagnosis was 25±36 months. At the disease onset, 20% of patients did not have small joint involvement (SJI). Seronegative patients tended to be female (p=0.001), had longer lag time (p=0.001), and had lower levels of C-reactive protein (p=0.025), white blood count (p=0.005), and neutrophil/lymphocyte ratio (p=0.001) compared to the dual seropositive group. Patients presenting with SJI had a younger age (p=0.002), tended to be female (p=0.001), and had lower RF (p=0.034) and anti-CCP (p=0.031) positivity. Only age (p=0.005) and dual seronegativity (RF and anti-CCP; p=0.035) were the independent predictors of SJI in multivariate analysis. The decreasing age and seronegative status were defined as independent risk factors of SJI at the onset of RA. Population-based, prospective studies are needed for earlier diagnosis.

Ultrasonographic Evaluation of the Ankle Joint in Relation to Rheumatoid Factor Status and Disease Activity in Patients with Rheumatoid Arthritis

Abstract Background: Rheumatoid arthritis (RA) is a form of inflammatory disease whose clinical pattern is largely dependent on the presence of both anti-citrullinated protein antibodies and rheumatoid factor (RF). Although this is still debatable, seronegative RA seems to be a somewhat less serious condition. The present study aimed to evaluate ankle joint ultrasound in relation to RF status and disease activity in RA patients. Methods: A cross-sectional study involving RA patients from a single center was conducted. Laboratory test evaluations and clinical activity assessments were carried out. The ankle joint was examined using musculoskeletal ultrasound (US). Results: The study included 100 patients with established RA in total. Eighty-two patients tested positive for RF with a mean age of 42.3, whereas only 18 tested negative with a mean age of 39.6. Patients who tested positive for RF had a longer duration of illness (9.39 ± 5.39 vs. 4.56 ± 3.24). There were no differences in clinical activity scores between the seropositive and seronegative groups. The pathological US findings of any ankle joint showed no differences between the seropositive and seronegative groups. Patients with US findings of tibialis posterior tenosynovitis in the left ankle and synovitis and erosion in the right ankle, particularly in the tibiotalar and talonavicular joints, had significantly high Disease Activity Score 28-Erythrocyte sedimentation rate-scores. The increased disease activity was accompanied by significant erosions on both ankles. Conclusion: In terms of disease activity, there is no clinically significant difference between seropositive and seronegative RA patients. Sonographic ankle joint abnormalities do not appear to be associated with the patients’ RF status. High RA disease activity, on the other hand, is associated with synovitis and erosions, particularly in the talonavicular and tibiotalar joints, as well as tibialis posterior tenosynovitis.

LEVELS OF C-REACTIVE PROTEIN AND TOTAL PROTEIN IN MALARIA AND HIV CO INFECTED PREGNANT WOMEN, ATTENDING THE ANTENATAL CLINIC OF NNAMDI AZIKIWE UNIVERSITY TEACHING HOSPITAL, NNEWI, SOUTHEASTERN NIGERIA.

The goal of the study was to quantify the levels of C reactive protein and protein in pregnant HIV-positive malaria-infected women. Pregnant women in HIV stages 1 and 2 who were 18 to 40 (36.98 + 5.49) years old participated in the study. The participant groups consisted of 80 HIV-positive pregnant women with 40 co-infected with malaria and 80 HIV-negative pregnant women with 40 co-infected with malaria. Blood samples were obtained from participants for the thick and thin film methods of counting and identifying malaria parasites and the immunochromatographic method of determining HIV status. The total protein content of the serum was determined using the Biuret method, and the violetcoloured solution that was produced was measured spectrophotometrically at 540 nm. The Enzyme linked Immunosorbent assay using the Human CRP kit method was employed to measure the level of CRP in the participants’ blood sample and the developed yellow coloured solution read at 450 nm using a spectrophotometer. In all cases, there was a statistically significant difference in protein and CRP levels between the HIV seropositive group with malaria infection (p&lt;0.05) and HIV seropositive group without malaria infection. The mean protein and CRP level of HIV-positive pregnant women who have malaria infection was statistically lower than that of HIV-positive pregnant women who do not have malaria but statistically higher than those of HIV-negative pregnant women with and without malaria infection. The study suggests that pregnant HIV-positive women do experience a heightened increase in protein and CRP levels majorly due to HIV. However, malaria infection also contributes to the level of increase seen in these parameters in pregnant women with the coinfection.