Revealing the distinct clinical patterns and relapse risk factors in seronegative IgG4-RD patients: A retrospective cohort study over a decade.

OBJECTIVES: Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients. METHODS: We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model. RESULTS: Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p < 0.0001), lower eosinophil count (p < 0.0001), lower serum IgE levels (p < 0.0001)), lower IgG4-RD responder index (RI) scores (p < 0.0001), and fewer affected organ numbers (p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse. CONCLUSIONS: Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.

Antibody profiles in the mosaic of "seronegative" APS syndrome.

Clinical manifestations, as distinct from thrombotic and obstetric morbidity, were recently included in the update of classification criteria of the antiphospholipid syndrome (APS). However, the existence of several patients with clinical manifestations suggestive of APS, but negative for criteria antiphospholipid antibodies (aPLs) [anti-cardiolipin antibodies (aCL), anti-ß2-glycoprotein I antibodies (aß2-GPI) and lupus anticoagulant] may suggest an update of diagnostic criteria. In this study, we analyzed the prevalence of six non-criteria aPLs in a large monocentric cohort of patients with seronegative APS (SN-APS), to investigate their possible diagnostic role. aCL IgA, aß2-GPI IgA and aß2-GPI Domain 1 antibodies were detected by chemiluminescence, anti-phosphatidylserine/prothrombin (aPS/PT) IgG, anti-vimentin/cardiolipin (aVim/CL) IgG and anti-carbamylated-ß2-glycoprotein I (aCarb-ß2-GPI) IgG by ELISA in sera from 144 SN-APS patients. In SN-APS patients, aCL IgA were detected in 4/144 (2.77%), aß2-GPI IgA in 2/144 (1.39%), aß2-GPI-Domain 1 in 1/144 (0.69%), aPS/PT in 16/144 (11.11%), aVim/CL in 37/144 (25.69%) and aCarb-ß2-GPI in 43/144 patients (29.86%). Patients negative for all non-criteria aPL assays were 77/144 (53.47%). Notably, the Venn diagram showed that aCarb-ß2-GPI together with aVim/CL represented the prevalent combination of positive antibodies. In SN-APS patients, aCL IgA were associated with recurrent thrombosis (OR11.48; p=0.03); in obstetric SN-APS patients, aPS/PT were significantly associated with foetal deaths (OR4.84; p=0.01), aVim/CL with spontaneous abortions (OR2.71; p=0.016). This study indicates that aPS/PT, aVim/CL and aCarb-ß2-GPI antibodies may represent useful tools to identify "seronegative" APS patients, who are negative for criteria aPLs, supporting the need to make testing for non-criteria aPLs more accessible in patients with SN-APS.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

Understanding the landscape of the SARS-CoV-2-specific T cells post-omicron surge.

Emerging evidence shows increased humoral response post-omicron surge, but research on T cell responses is limited. This study investigated the durability, magnitude, and breadth of SARS-CoV-2-spike-specific T cell responses in 216 two-dose vaccinated individuals pre- and post-omicron surge. Post-surge samples showed enhanced T cell responses, indicating widespread asymptomatic exposure to omicron. Further analysis of 105 individuals with multiple exposures to SARS-CoV-2 through boosters or infections showed that post-omicron, two-dose vaccinated individuals had T cell responses comparable to those of COVID-19 convalescents or boosted individuals. Additionally, we report cross-reactive T cell responses against omicron sub-variants, including BA2.86, remained strong, with preserved frequencies of spike-specific stem-cell-like memory T cells. In silico prediction indicates that mutated epitopes of JN.1 and KP.2 retain over 95.6% of their HLA binding capability. Overall, our data suggests that T cell responses are sustained, enhanced, and cross-reactive against emerging SARS-CoV-2 variants following symptomatic or asymptomatic omicron infection.

Elevated levels of anti-Golgi antibodies: An early sign of seronegative rheumatoid arthritis.

Anti-Golgi antibodies are uncommon antibodies that exhibit specific, polarized cytoplasmic staining on the Hep-2 substrate. The objective of our study was to identify the clinical and laboratory features associated with anti-Golgi antibodies. We examined 4.5 years of data from a Turkish tertiary hospital in this retrospective cohort analysis. The indirect immunofluorescence staining patterns, antinuclear antibody (ANA) titres and clinical data of all patients were obtained from the hospital record system. A total of 146,055 ANAs were detected, of which 224 patients (0.15%) exhibited anti-Golgi antibody staining. In total, 39.4% of diagnosed patients had autoimmune diseases (AIDs). Of the AIDs, 26 (46.4%) were rheumatoid arthritis (RA). This is a very high rate and another remarkable point is that 17 (65.3%) of these patients had seronegative RA. High-titre results (1 ≥ 1/320) were more common in patients with AID. Anti-Ro52 was prevalent in 50% of extractable nuclear antigen (ENA)-positive patients, making it a remarkable finding. The majority of individuals with high-titre anti-Golgi antibodies had AID, particularly RA. The majority of these patients also tested negative for anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF). Finally, high-titre anti-Golgi antibodies may be an important serologic marker for seronegative RA in the Turkish population.

The absence of antibodies in longitudinally extensive transverse myelitis may predict a more favourable prognosis.

BACKGROUND: Isolated first episodes of longitudinally extensive transverse myelitis (LETM) have typically been associated with neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, in some cases, serological testing and screening for other aetiologies are negative, a condition referred to as double seronegative longitudinally extensive transverse myelitis (dsLETM). OBJECTIVE: The objective of this study was to evaluate comparative outcomes of dsLETM, MOGAD-LETM and NMOSD-LETM. METHODS: Cohort study of LETM cases seen in the UK NMOSD Highly Specialised Service between January 2008 and March 2022. RESULTS: LETM = 87 cases were identified (median onset age = 46 years (15-85); median follow-up = 46 months (1-144); 47% NMOSD-LETM = 41 (aquaporin-4 antibodies (AQP4-IgG) positive = 36), 20% MOGAD-LETM = 17 and 33% dsLETM = 29). Despite similar Expanded Disability Status Scale (EDSS) at nadir, last EDSS was higher in AQP4-IgG and seronegative NMOSD-LETM (sNMOSD) (p = 0.006). Relapses were less common in dsLETM compared to AQP4-IgG NMOSD-LETM and sNMOSD-LETM (19% vs 60% vs 100%; p = 0.001). Poor prognosis could be predicted by AQP4-IgG (odds ratio (OR) = 38.86 (95% confidence interval (CI) = 1.36-1112.86); p = 0.03) and EDSS 3 months after onset (OR = 65.85 (95% CI = 3.65-1188.60); p = 0.005). CONCLUSION: dsLETM remains clinically challenging and difficult to classify with existing nosological terminology. Despite a similar EDSS at nadir, patients with dsLETM relapsed less and had a better long-term prognosis than NMOSD-LETM.

Clinical characteristics and treatment outcomes in patients with double-seronegative myasthenia gravis.

BACKGROUND AND PURPOSE: Double-seronegative myasthenia gravis (dSNMG) is defined as myasthenia gravis (MG) without detectable or low affinity antibodies to acetylcholine receptor (AChR) and muscle-specific kinase (MuSK). There are limited data on detailed clinical features and outcomes after treatment in dSNMG patients. The aim was to describe the clinical characteristics and outcomes in dSNMG patients based on MG scales. METHODS: A retrospective study was performed of patients diagnosed with MG who had negative AChR or MuSK antibodies and they were compared with an AChR-positive MG cohort. Correlations were made with data from the first and last clinic visits, between demographics, clinical characteristics, treatment and disease severity, based on the Myasthenia Gravis Foundation of America category, Myasthenia Gravis Impairment Index (MGII), Patient Acceptable Symptom State and simple single question (SSQ). RESULTS: Eighty patients met the inclusion criteria for dSNMG. The baseline MGII and SSQ scores in the dSNMG cohort showed no significant differences from the AChR group (p = 0.94 and p = 0.46). The dSNMG cohort MGII and SSQ scores improved significantly at the last clinical evaluation (p = 0.001 and p = 0.047). The MGII improvement in the AChR cohort was significantly better (p = 0.003). CONCLUSIONS: The initial severity of dSNMG based on clinical scores is similar to antibody-positive MG patients. There is significant clinical improvement in dSNMG patients after therapy, measured in the last clinical evaluation. This supports an immune pathophysiology of many dSNMG patients.

Acetylsalicylic acid inhibition of the lipoxygenase pathway: Implications for HIV prevention.

BACKGROUND: 1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown. METHODS: Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA. CONCLUSIONS: Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.

Heightened migraine risk in patients with rheumatoid arthritis: A national retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database. BACKGROUND: Migraine may be related to immune dysfunction and previous studies have suggested an association with chronic inflammatory rheumatic diseases; however, the relationship between RA and migraine remains unclear. METHODS: This was a population-based, nationwide, retrospective, longitudinal cohort study. Participants were enrolled from 2010 to 2017 and followed up until 2019. A total of 42,674 patients who had undergone a health checkup within 2 years prior to the initial diagnosis of RA were included in the study, after applying the exclusion criteria (previous migraine, other rheumatic disease, missing variables of interest). A non-RA control was obtained by age and sex-matching (1:5). Finally, 42,644 patients with RA were enrolled, with 213,370 individuals without RA included as controls. Among the patients with RA, 29,744 had seropositive RA (SPRA), and 12,900 had seronegative RA (SNRA). SPRA was defined by the International Classification of Diseases 10th revision (ICD-10) code M05, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and enrollment in a special copayment reduction program. SNRA was defined by the ICD-10 code M06 and prescription of any DMARD. The primary endpoint was the occurrence of migraine incidents, defined using the ICD-10 code of migraine (G43). RESULTS: A total of 22,294 migraine cases (17,912/213,370 [8.3%] in controls and 4382/42,674 [10.2%] in RA) were reported during a mean follow-up of 4.4 years after a 1-year lag period. Patients with RA had a 1.2-fold higher risk of migraine compared with controls (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.17-1.26). Increased risk of migraine was found in both patients with SNRA and SPRA compared with controls (aHR 1.20, CI 1.15-1.24 in SPRA; aHR 1.26, CI 1.19-1.34 in SNRA). Compared to patients with SNRA, those with SPRA did not demonstrate a heightened risk (aHR 0.94, CI 0.88-1.01). A significant interaction was confirmed between covariates (male, current smoker, those with diabetes mellitus, and dyslipidemia) and the risk of migraine (p for interaction of <0.05). CONCLUSION: RA was linked to a higher migraine risk, regardless of seropositivity.

Seronegative brucella meningitis diagnosed by CSF PCR: report on seven cases.

INTRODUCTION: Neurobrucellosis (NB) can be associated with meningitis and present as a headache with or without meningeal signs. Pseudotumor presentation of NB has been reported to be accompanied by lymphocytic predominant cerebrospinal fluid(CSF) pleocytosis. NB is diagnosed by means of isolation of Brucella from blood or CSF and/or the presence of anti-Brucella antibodies in the CSF. Molecular techniques have been used in chronic or challenging cases of NB. CLINICAL FINDINGS: We report on seven cases of NB presenting with different types of headache and signs of meningeal involvement. In five cases, signs of intracranial hypertension were evident in the form of papilledema, sixth nerve palsy and blurred vision. DIAGNOSIS: MRIs of the brain revealed signs of intracranial hypertension in three patients, basal meningeal enhancement in one patient and white matter lesions in one patient. Brucella serology in the blood and CSF was negative in all patients. It was interesting that four patients had normocellular CSF analysis with normal glucose and protein results. The diagnosis was made by Brucella PCR in all patients. CONCLUSION: NB should be considered in the differential diagnoses of pseudotumor cerebri syndrome in endemic areas. It is important to employ molecular techniques using sterile CSF samples in the investigation of Brucella.

Predictors of Subsequent Celiac Disease Seropositivity in Patients Diagnosed with Duodenal Villus Atrophy on Upper Endoscopy.

BACKGROUND: The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on duodenal biopsies in patients without prior CD serologies. AIMS: To characterize the predictors of CD seropositivity in patients with VA on biopsy without prior CD serologies. METHODS: We performed a retrospective cohort study of patients found to have duodenal VA on histopathology from 2010 to 2020 who did not have prior CD serologies measured and who had them checked after their biopsy. Patients with known or suspected CD prior to their duodenal biopsy were excluded. RESULTS: Of 162 patients with VA and no prior CD serologies, 50 (31%) subsequently had an elevated TTG IgA consistent with CD. Patients with an elevated TTG IgA were more likely to be non-Hispanic (76% vs. 42%; p < 0.001), white (74% vs. 62%; p = 0.025), and younger (ages 18-39, 26% vs. 12%; p = 0.002) compared to those with a negative TTG IgA. By contrast, these patients were less likely to present in middle adulthood (ages 40-59, 6% vs. 29%; p =  0.002). The most common identified etiologies of seronegative VA were Crohn's disease (13%), seronegative CD (8.9%), H. pylori infection (6.3%), tropical sprue (5.4%), and olmesartan-related enteropathy (3.6%). CONCLUSION: Age and ethnicity may be helpful when stratifying the likelihood of CD in the absence of supporting serologies. A majority of patients (69%) diagnosed with VA without prior CD serologies have negative serologies, consistent with seronegative CD or the spectrum of non-celiac enteropathies for which further evaluation is needed.

Clinical features of double seronegative ocular myasthenia gravis.

PURPOSE: To clarify the clinical features of patients with Double seronegative (DS) ocular myasthenia gravis (OMG). METHODS: Sixty-one patients diagnosed with DS OMG at the Department of Ophthalmology, Hyogo Medical University Hospital over a 5-year period from 2017 were included. Patients were classified into three groups based on the initial examination findings: group P (ptosis alone), group M (ocular motility disorder alone), and group PM (combination of both). We retrospectively reviewed the patients and clarified their clinical features. RESULTS: There were 32 males and 29 females, with a mean age of 49.8 ± 20.9:1-82 years. Twenty-one patients (34.4%) were in group P, 23 (37.7%) in group M, and 17 (27.8%) in group PM. The proportion of males (73.9%) was significantly higher in group M compared with the other two groups. The diagnosis was proven by detection of neuromuscular junction (NMJ) disorder in 73.8%, oral pyridostigmine trial test in 13.1%, and eight patients (13.1%) in group M were diagnosed after surgical treatment. The clinical symptoms were resolved by oral pyridostigmine treatment in 54.1% of cases. CONCLUSION: About 30% of patients with DS OMG had no obvious NMJ disorder, and an oral pyridostigmine trial test was necessary to diagnose these patients. Although DS OMG is often considered as the mildest form of MG, its prognosis is not optimistic and it requires aggressive therapeutic intervention. TRIAL REGISTRATION: Trial registration number: 202104-750, "2016/4/18," retrospectively registered.

Seronegative HIV-1 infection in a Japanese man presenting with Pneumocystis pneumonia: Analysis of long-term antibody response and literature review.

Seronegative human immunodeficiency virus (HIV) infection, where an HIV-specific antibody response is lacking even in chronic or late-stage HIV infections, is extremely rare. Here, we report the case of a 50-year-old Japanese man presenting with Pneumocystis pneumonia who did not produce antibodies against HIV-1 until the initiation of antiretroviral therapy (ART). Fourth-generation antigen-antibody testing temporarily reverted from weakly positive to negative soon after initiating ART, likely due to a reduction in viral load (assessed by p24 antigen levels). His HIV-1 antibody titers remained low or indeterminate even after four years of ART. A literature review suggested that the absence of HIV-1-specific antibody production may be associated with unimpeded HIV replication and rapid CD4+ T cell decline. Seronegative HIV infection can lead to deferred diagnosis and treatment, thereby increasing the risk of transmitting the virus to others or developing opportunistic illnesses. It is important to combine multiple tests for diagnosis, depending on the medical condition. Further studies are required to investigate the host factors involved in the production of HIV-1-specific antibodies.

Outcomes of Total Hip Arthroplasty in Seronegative Spondyloarthropathies: A Propensity-Matched Cohort Analysis.

INTRODUCTION: Total hip arthroplasty (THA) is a common surgical intervention for patients who have seronegative spondyloarthropathies (SpA). However, there is a paucity of literature addressing the outcomes of THA specifically in SpA patients. This study aimed to investigate both the short- and long-term systemic and orthopaedic outcomes of THA in SpA patients as a whole, as well as within the individual subtypes of SpA. METHODS: This retrospective cohort study utilized a federated health research network, identifying 3,074 SpA patients who underwent THA between 2005 and 2022. Propensity score matching was used to compare SpA and non-SpA patients, balancing baseline characteristics. Short-term (30-day, 180-day, 1-year) and long-term (5-year) postoperative complications were analyzed. The outcomes included systemic and joint complications. Chi-square analyses were done to compare outcomes across categorical data. RESULTS: The SpA patients had increased rates of revision THA, prosthetic dislocation, periprosthetic joint infection, and aseptic loosening at various postoperative intervals. Surgical site infections and myocardial infarctions were more frequent at one month, six months, and one year. Additionally, SpA patients exhibited a higher incidence of deep vein thrombosis at six months and one year. Subtype analysis revealed that ankylosing spondylitis patients were more likely to have revision surgery and prosthetic dislocation, while Psoriatic Arthritis patients had a lower risk of hip dislocation and femur fractures. CONCLUSION: The SpA patients undergoing THA are at greater risk for systemic and orthopaedic complications compared to non-SpA patients. The increased incidence of infections, thromboembolic events, and prosthetic issues highlight the need for careful preoperative assessment and postoperative management.

Application of Salivary Alpha-1 Antitrypsin in the Diagnosis of Rheumatoid Arthritis: A Pilot Study.

Background and Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually destroyed. Early diagnosis and treatment before joint deformation or destruction is important. The detection of novel RA biomarkers in saliva may facilitate early detection of RA before disease onset. This study aimed to evaluate salivary concentration of α1-antitrypsin (A1AT) in healthy patients and those with RA, and to assess the diagnostic value of salivary A1AT. Materials and Methods: In total, 80 participants were included: 20 healthy participants, and 60 patients with RA. Saliva and serum samples were obtained from all the patients. Levels of A1AT and cytokines, including interleukin-1 beta (IL-1ß), IL-6, and IL-10 in saliva and serum, were evaluated using an enzyme-linked immunosorbent assay kit and Luminex assay. Data were analyzed using SPSS for Windows. Results: There was a higher level of A1AT in the saliva of patients with RA (median: 2388.66 ng/mL) than that in healthy controls (1579.06 ng/mL). There was a positive mild-to-moderate accuracy (area under the curve: 0.57-0.85) of A1AT in saliva to diagnose RA. The cut-off level (ng/mL) of A1AT in saliva for detecting RA was 1689.0. Conclusions: The obtained data can promote the application of the measurements of A1AT in saliva to diagnose RA.

Clinical profile and challenges faced in the management of optic neuritis: the Indian scenario.

PURPOSE: Optic neuritis (ON) is a relatively common ophthalmic disease that has recently received renewed attention owing to immunological breakthroughs. We studied the profile of patients with ON with special reference to antibody-mediated ON and the challenges faced in its management. METHODS: Case records of patients with ON presenting to a tertiary eye-care center in South India were analyzed. Data on demographics, presenting visual acuity (VA), clinical features, seropositivity for aquaporin-4 immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), details of magnetic resonance imaging (MRI) of orbits and brain, and treatment were collected. RESULTS: Among 138 cases with acute ON, male: female ratio was 1:2. Isolated ON was present in 41.3% of cases. Antibody testing of sera was performed in 68 patients only due to financial limitations. Among these, 48.5% were MOG-IgG-seropositive, 11.76% were AQP4-IgG-seropositive, and 30.88% samples were double seronegative. Other causes included multiple sclerosis (n = 4), lactational ON (n = 4), tuberculosis (n = 2), invasive perineuritis (n = 2), COVID-19 vaccination (n = 2), and COVID-19 (n = 1). The mean presenting best corrected visual acuity (BCVA) was 1.31 ± 1.16 logMAR (logarithm of the minimum angle of resolution). The mean BCVA at 3 months was 0.167 ± 0.46 logMAR. Only initial VA ≤ 'Counting fingers' (CF) had a significant association with the visual outcome for final VA worse than CF. The steep cost of investigations and treatment posed challenges for many patients in the management of ON. CONCLUSION: MOG-IgG-associated ON is common in India. Unfortunately, financial constraints delay the diagnosis and timely management of ON, adversely affecting the outcome.

Clinical Features of ACPA-Negative and ACPA-Positive Variants of Rheumatoid Arthritis.

The aim of the study was to investigate the features of the clinical picture of the disease in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis. MATERIALS AND METHODS: : The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the ACPA values, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease, and therapy. The nature of the onset and course of the disease and the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices). RESULTS AND DISCUSSION: : The study involved 79 patients with ACPA-negative variant of RA and 79 ACPA-positive patients. The age of patients (Me [IR] (in years)) with the ACPA(-) variant was 52 [39; 62]; with the ACPA(+) variant, 54 [42; 62]; the duration of the disease (in months) was 59 [23; 122] and 48 [17; 84], respectively. In ACPA(+) patients, a higher disease activity was determined (by the indices DAS 28crp, DAS28esr, SDAI, CDAI), higher values of C-reactive protein and erythrocyte sedimentation rate, and a greater number of painful and swollen joints (p < 0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(-) (17.7%) patients. Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, whereas a tendency to a higher frequency of neuropathy, sclerites, and episcleritis was revealed in ACPA(-) patients. CONCLUSIONS: . In patients with ACPA(-) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less "bright" course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.

Anti-Carbamylated Protein Antibodies in ACPA-Negative and ACPA-Positive Patients with Rheumatoid Arthritis.

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis. MATERIALS AND METHODS: . The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL). RESULTS AND DISCUSSION: . Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(-) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691-0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%. In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(-) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(-) RA group. CONCLUSIONS: . We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(-) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more "erosive" subtype of the disease than ACPA(+) anti-CarP(-) patients. In ACPA(-) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(-) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases.

Recurrent simultaneous central nervous system demyelination with possible peripheral demyelination / nodopathy in a seronegative patient.

Combined central and peripheral demyelination (CCPD) is a rare disease entity. Onset with the simultaneous central nervous system (CNS) and peripheral nervous system (PNS) involvement and its recurrence are exceptional. Anti-neurofascin antibodies have been shown to be present in up to 70% of cases, yet seronegative patients also exist. We present a case of seronegative recurrent CCPD. The PNS involvement was compatible with two episodes of recurrent Guillain-Barre syndrome (GBS), whereas the CNS involvement pattern was not typical for either multiple sclerosis (MS) or acute disseminated encephalomyelitis. The prognosis was excellent with pulse methylprednisolone, intravenous immunoglobulin, and plasmapheresis. This case highlights the varied clinical presentations of CCPD, extending beyond the realms of MS and chronic inflammatory demyelinating polyneuropathy, and underscores the potential for relapse. Importantly, to the best of our knowledge, this represents the inaugural instance of CCPD featuring PNS involvement in the form of recurrent GBS.

Targeting the serum marker interleukin 9 improves the underlying characterization and immune homeostasis in rheumatoid arthritis.

Introduction: Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are serological markers used for diagnosing rheumatoid arthritis (RA), an autoimmune disease characterized by inflammatory joint damage. However, there is a subset of RA patients who test negative for both RF and ACPA, known as seronegative rheumatoid arthritis (SNRA). Material and methods: The levels of serum markers were examined in both clinical samples and a rat model of type II collagen-induced RA (CIA). The effect of interleukin 9 (IL-9) on RA was investigated using recombinant rat IL-9 (rrIL-9), anti-rat IL-9 neutralizing monoclonal antibody (mAb), and control IgG antibody in the CIA rat. The severity of arthritis was assessed. Treg and Th17 cells, M1 and M2 macrophages, and inflammatory cytokine levels were analyzed. Results: We observed higher levels of IL-9 in clinical samples from SNRA patients compared to the normal group. Rat models of CIA exhibit increased arthritis scores, weight loss, paw swelling, and severe joint damage. IL-9 was the most sensitive serum marker for the diagnosis of RA in serum assays of CIA rats. IL-9 increased arthritis scores and cartilage damage, whereas treatment with IL-9 inhibitors produced the opposite effect. IL-9 inhibitors promoted Treg/Th17 homeostasis, decreased M1 macrophages, increased M2 macrophages, and decreased levels of inflammatory cytokines in joint tissues. Conclusions: These results suggest that IL-9 has potential as a diagnostic marker for SNRA. Inhibition of IL-9 could reduce the severity of arthritis in CIA rats by ameliorating inflammation and modulating the Treg/Th17 immune balance, M2 and M1 macrophage activation.