New-onset atrial fibrillation in seropositive rheumatoid arthritis: association with disease-modifying anti-rheumatic drugs treatment.

OBJECTIVE: Atrial fibrillation (AF) is a potentially lethal complication that leads to increased hospitalization, disability and mortality. Furthermore, the risk of cardiovascular disease is increased in RA. We evaluated whether DMARD treatment is associated with incident AF in patients with seropositive RA (SPRA). METHODS: The South Korean Health Insurance Review and Assessment Service database was used to identify patients newly diagnosed with SPRA between 2010 and 2020. A nested case-control analysis was performed to match AF-affected patients to unaffected controls for age, sex, follow-up duration, and index year of SPRA diagnosis at a 1:4 ratio. Adjusted conditional logistic regression was used to identify the predictive factors for AF. RESULTS: Of the 108 085 patients with SPRA, 2,629 (2.4%) developed new-onset AF, and the proportion of females was ∼67%. In the matched population, pre-existing comorbidities of hypertension, chronic kidney disease, and heart failure were associated with increased risk of AF. Meanwhile, the use of methotrexate (MTX) decreased the risk of incident AF [adjusted odds ratio (aOR), 0.89], whereas the use of leflunomide (LEF) increased AF (aOR, 1.21). In a subgroup of patients aged ≥50 years, LEF and adalimumab increased the occurrence of AF, while MTX decreased AF in males and LEF increased this risk in females. CONCLUSION: Although the number of subjects developing new-onset AF was small, MTX decreased and LEF increased incident AF in patients with RA. Especially, a distinct pattern of AF risk with DMARDs usage was observed according to age and sex.

Incidence of septic arthritis in patients with ankylosing spondylitis and seropositive rheumatoid arthritis following TNF inhibitor therapy.

OBJECTIVES: Septic arthritis (SA) is a serious complication occurring in the joints, and its risk increases with immunosuppressive therapy. This study investigated whether TNF inhibitors increase the risk of SA in patients with AS and seropositive RA (SPRA). METHODS: We searched the South Korean Health Insurance Review and Assessment Service database for incident cases of AS and SPRA between 2010 and 2020. SA was defined using the diagnostic code M00 and hospital admission. Cox-proportional hazards analysis was conducted to compare the incidence of SA according to TNF inhibitor (infliximab, etanercept, adalimumab/golimumab) use during follow-up. RESULTS: Of the 145 129 patients analysed, 1170 (0.8%) developed SA during the follow-up period. Older age; male sex; SPRA diagnosis; comorbidities of hypertension (HTN), diabetes mellitus (DM) and chronic pulmonary disease (CPD); and infliximab and etanercept use increased the incidence of SA in the overall population. However, in patients with AS, only age and renal disease were predictors of SA, and TNF inhibitors did not increase the incidence of SA. Meanwhile, patients with SPRA treated with TNF inhibitors were prone to SA regardless of TNF inhibitor type, and age, HTN, DM and CPD were associated with SA. The incidence of SA was prominent after the first year of commencing TNF inhibitor therapy, for both AS and SPRA. CONCLUSION: TNF inhibitors increase the incidence of SA, specifically in patients with SPRA, but not AS. Importantly, age, comorbidities and the early time period after starting TNF inhibitors were associated with SA, which should be considered simultaneously when initiating TNF inhibitor therapy.

FLT3 functional low-frequency variant rs76428106-C is associated with susceptibility to systemic sclerosis.

OBJECTIVES: rs76428106-C, a low frequency polymorphism that affects the splicing of the FLT3 gene, has recently been associated with several seropositive autoimmune diseases. Here, we aimed to evaluate the potential implication of rs76428106-C in the susceptibility to systemic sclerosis (SSc). METHODS: We analysed a total of 26 598 European ancestry individuals, 9063 SSc and 17 535 healthy controls, to test the association between FLT3 rs76428106-C and SSc and its different subphenotypes. Genotype data of rs76428106 were obtained by imputation of already available genome-wide association study data and analysed by logistic regression analysis. RESULTS: In accordance with that observed in other autoimmune disorders, the FLT3 rs76428106-C allele was significantly increased [P-value = 2.03 × 10-3, odds ratio (OR) = 1.34] in SSc patients compared with healthy controls. A similar risk effect was found when the main SSc clinical and serological subgroups were compared with controls. When comparing SSc patients with and without digital ulcers (DU), the rs76428106-C frequency was significantly increased in DU-positive SSc patients in comparison with DU-negative patients (P-value = 0.036, OR = 2.16). CONCLUSION: This study is the first to report an association between rs76428176-C and SSc. Our results support the role of FLT3 as a relevant gene in seropositive immune-mediated diseases and a potential biomarker for SSc microangiopathy.

A systematic review and meta-analysis of the prevalence of human cytomegalovirus shedding in seropositive pregnant women.

The detection of human cytomegalovirus (HCMV) in an individual's bodily fluid by culture techniques or through HCMV DNA detection by polymerase chain reaction, is known as HCMV shedding. Human cytomegalovirus shedding has the potential to transmit HCMV infection, where an individual can become infected with HCMV through contact with the bodily fluid of another individual containing HCMV. Human cytomegalovirus shedding can occur in primary infection and in non-primary infection for individuals with prior infection (HCMV seropositive). Human cytomegalovirus infection causes few or no symptoms in a pregnant woman, but can cause significant harm to her foetus if congenital CMV (cCMV) infection occurs. The association between HCMV shedding in HCMV seropositive pregnant women and the vertical transmission of HCMV to result in cCMV infection is poorly investigated, challenged by a limited understanding of the distribution of HCMV shedding in HCMV seropositive pregnant women. We systematically reviewed the published literature to describe the prevalence of HCMV shedding in HCMV seropositive women during pregnancy up to delivery. This analysis identified nine studies that met our eligibility criteria. In these studies, the prevalence of HCMV shedding in any bodily fluid of HCMV seropositive women during pregnancy and at delivery ranged from 0% to 42.5%. A meta-analysis, performed on six of the nine studies with suitable sample sizes, estimated a pooled prevalence of 21.5% [95% CI 12.7%,30.3%]. To our knowledge, this is the first review to systematically search the literature to summarise the prevalence of HCMV shedding in HCMV seropositive pregnant women. These estimates can help in the development of disease burden models and therapeutic or preventative strategies against cCMV infection in the context of non-primary maternal HCMV infection.

Relationship between gluten availability and celiac disease prevalence: A geo-epidemiologic systematic review.

Celiac disease is a global disease requiring genetic susceptibility and gluten exposure to trigger immune-mediated enteropathy. The effect of the degree of gluten-containing grain availability on celiac disease prevalence is unknown. Our objective was to compare country-based gluten availability to celiac prevalence using a systematic literature review. We searched MEDLINE, Embase, Cochrane, and Scopus until May 2021. We included population-based serum screening with confirmatory testing (second serological study or small intestine biopsy) and excluded specific, high-risk, or referral populations. We determined country-specific gluten availability using the United Nations food balance for wheat, barley, and rye. Human leukocyte antigen (HLA) frequencies were obtained from allelefrequencies.net. The primary outcome was association between gluten-containing grain availability and celiac disease prevalence. Generalized linear mixed models method with Poisson's link was used for analysis. We identified 5641 articles and included 120 studies on 427 146 subjects from 41 countries. Celiac disease prevalence was 0-3.1%, median 0.75% (interquartile range 0.35, 1.22). Median wheat supply was 246 g/capita/day (interquartile range 214.8, 360.7). The risk ratio (RR) for wheat availability on celiac disease was 1.002 (95% confidence interval [CI]: 1.0001, 1.004, P = 0.036). A protective association was seen with barley, RR 0.973 (95% CI: 0.956, 0.99, P = 0.003), and rye, RR 0.989 (95% CI: 0.982, 0.997, P = 0.006). The RR for gross domestic product on celiac disease prevalence was 1.009 (95% CI: 1.005, 1.014, P < 0.001). The RR for HLA-DQ2 was 0.982 (95% CI: 0.979, 0.986, P < 0.001), and that for HLA-DQ8 was 0.957 (95% CI: 0.950, 0.964, P < 0.001). In this geo-epidemiologic study, gluten-containing grain availability showed mixed associations with celiac disease prevalence.

Incidence of seropositive rheumatoid arthritis in population-based studies in Northern Savo, Finland, during 1980-2020.

The objective is to evaluate the incidence of seropositive rheumatoid arthritis (RA) over 40-year period in Northern Savo, Finland. Data on new seropositive RA patients according to the American College of Rheumatology (ACR) 1987 classification criteria were collected in 2020-2021. In 2020 data on tobacco exposure, patient-reported dental health and living in residences with fluoridated tap water were gathered. Incidence rates were estimated and age- and gender-adjusted to Northern Savo population. The results were compared with data acquired in studies from 1980, 1990, 2000, and 2010. In 2020, 46 seropositive RA patients (21 females and 25 males) were recorded. The crude incidence of seropositive RA fulfilling the ACR 87 criteria in 2020 was 22.3 (95% CI 16.3 to 29.8)/100 000 and age and gender-adjusted 22.3 (95% CI 15.9 to 28.8)/100 000. Tobacco exposure > 5 pack years occurred 18% of females and 56% of males. Only 16% of males were full dentate. A total of 242 incident seropositive RA (age ≥ 16 years, 55% females) were identified in all study years. No differences in the gender-specific incidence rates in each cohort or in incidence between the studies every 10 years were recorded. The incidence of seropositive RA decreased in the age group < 55 years, p = 0.003. There was no change in the incidence of seropositive RA between genders or the study years. A declining trend for occurrence of seropositive RA in the young and early middle-aged population may reflect change in risk factors.

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months.

BACKGROUND: Respiratory syncytial virus (RSV) remains a leading cause of pediatric morbidity, with no approved vaccine. We assessed the safety and immunogenicity of the Ad26.RSV.preF vaccine candidate in adults and children. METHODS: In this randomized, double-blind, phase 1/2a, placebo-controlled study, 12 adults (18-50 years) and 36 RSV-seropositive children (12-24 months) were randomized 2:1 to Ad26.RSV.preF (1 × 1011 viral particles [vp] for adults, 5 × 1010 vp for children) or placebo, at day 1 and 29, with 6-month immunogenicity and 1-year safety follow-up. Respiratory syncytial virus infection was an exploratory outcome in children. RESULTS: In adults, solicited adverse events (AEs) were generally mild to moderate, with no serious AEs. In children, no vaccination-related serious AEs were reported; fever was reported in 14 (58.3%) Ad26.RSV.preF recipients. Baseline pediatric geometric mean titers for RSV A2 neutralization increased from 121 (95% confidence interval [CI], 76-191) to 1608 (95% CI, 730-3544) at day 29, and 2235 (95% CI, 1586-3150) at day 57, remaining elevated over 7 months. Respiratory syncytial virus infection was confirmed in fewer children receiving Ad26.RSV.preF (1, 4.2%) than placebo (5, 41.7%). CONCLUSIONS: Ad26.RSV.preF demonstrated immunogenicity in healthy adults and toddlers, with no safety concerns raised. Evaluations in RSV-seronegative children are underway.

Clinical Spectrum of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Protection From Symptomatic Reinfection.

BACKGROUND: There are few data on the full spectrum of disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across the lifespan from community-based or nonclinical settings. METHODS: We followed 2338 people in Managua, Nicaragua, aged <94 years from March 2020 through March 2021. SARS-CoV-2 infection was identified through real-time reverse transcription polymerase chain reaction (RT-PCR) or through enzyme-linked immunosorbent assay. Disease presentation was assessed at the time of infection or retrospectively by survey at the time of blood collection. RESULTS: There was a large epidemic that peaked between March and August 2020. In total, 129 RT-PCR-positive infections were detected, for an overall incidence rate of 5.3 infections per 100 person-years (95% confidence interval [CI], 4.4-6.3). Seroprevalence was 56.7% (95% CI, 53.5%-60.1%) and was consistent from age 11 through adulthood but was lower in children aged ≤10 years. Overall, 31.0% of the infections were symptomatic, with 54.7% mild, 41.6% moderate, and 3.7% severe. There were 2 deaths that were likely due to SARS-CoV-2 infection, yielding an infection fatality rate of 0.2%. Antibody titers exhibited a J-shaped curve with respect to age, with the lowest titers observed among older children and young adults and the highest among older adults. When compared to SARS-CoV-2-seronegative individuals, SARS-CoV-2 seropositivity at the midyear sample was associated with 93.6% protection from symptomatic reinfection (95% CI, 51.1%-99.2%). CONCLUSIONS: This population exhibited a very high SARS-CoV-2 seropositivity with lower-than-expected severity, and immunity from natural infection was protective against symptomatic reinfection.

Current intimate partner violence and associated factors among sero-positive women attending Adama town ART Clinics, Central Ethiopia 2019.

BACKGROUND: Intimate partner violence against women is a behavior within an intimate relationship that causes physical, sexual, or psychological harm to the victim. It is well recognized as a gross violation of human rights and affects the health of women, families, and the community at large. However, the level to which Human Immuno Deficiency virus sero-positive women are experiencing recent intimate partner violence and its associated factors have not been well investigated as the majority of the study done so far were focused on the study of lifetime violence and violence among women in the general population. The study was conducted to determine the prevalence and factors associated with current intimate partner violence among sero-positive women. METHODS: A facility-based cross-sectional study was conducted from March 2019 to April 2019 among 396 sero-positive women visiting anti-retroviral therapy (ART) units of Adama town public health facilities. A systematic random sampling technique was used to select individual participants. Validated World Health Organization (WHO) tools were used to collect information on the outcomes and key independent variables. The collected data were entered into Epidata version 4.4.6 and analyzed using SPSS version 24. Descriptive statistics were used to compute summary statistics and proportion. Variables at a cut-off value of 0.25 on bivariate analysis and 0.05 during multivariate logistic regression were used to identify factors associated with recent intimate partner violence. RESULT: The response rate in this study was 100% since all women approached took part in this study. The prevalence of current intimate partner violence was 32.3% while lifetime intimate partner violence (IPV) was 45.5%. Exposure to coerced first sexual intercourse [AOR = 3.0 (1.73, 5.44)], male multi-partnership [AOR = 2.2 (1.21, 4.06)], believing in the husband's right to sex [AOR = 2.3 (1.29, 4.12)], contraceptive use [AOR = 3.33 (1.67, 6.62)], and having farmer partner [AOR = 3.9 (1.43, 10.79)] were significantly associated with current intimate partner violence. CONCLUSION: One-in-three women reported at least 2 or more forms of violence from their intimate partner. Individual-level factors (Exposure to coerced first sexual intercourse, partner's occupation, contraceptive use, and believing in husband's right to sex and relationship factor (Male multi-partnership) were significantly associated with recent intimate partner violence. Combined efforts are required to avert intimate partner violence among women on ART while targeting risky sexual behavior practiced among male partner factors significantly associated with violence.

Leptospira seroprevalence and associated risk factors in healthy Swedish dogs.

BACKGROUND: Leptospirosis is an emerging zoonotic infection worldwide and a cause of life-threatening disease in dogs. Seroprevalence in Swedish dogs is unknown. The aims of the present study were to estimate seroprevalence of pathogenic Leptospira in healthy dogs in Sweden using the microagglutination test (MAT) and a rapid point-of-care enzyme-linked immunosorbent assay (ELISA), and to evaluate risk factors of Leptospira exposure in Swedish dogs. RESULTS: Positive MAT titres (≥ 1:50) were detected in 27/369 (7.3%) of included dogs. Five different serovars were represented of which the Saxkoebing serovar was the most common (64.3%), followed by Copenhagi (14.3%), Bratislava (10.7%), Icterohaemorrhagiae (7.1%), and Canicola (3.6%). The ELISA test (SNAP® Lepto) was positive in 3/316 (0.9%) dogs. Living in urban areas and contact with stagnant water were found to be risk factors for Leptospira seropositivity (p < 0.05) in a multivariable logistic regression model. CONCLUSION: In this first seroprevalence study of Leptospira in Swedish dogs, it was shown that healthy dogs without recent (24 months) travel history and antileptospira vaccination had been exposed to pathogenic Leptospira interrogans serovars. Contact with stagnant water and living in urban areas were independent risk factors for seropositivity.

Trend in seroprevalence of SARS-CoV-2 (IgG antibody) among tribal-dominated population: Findings from Jharkhand, India.

Background & objectives: Serosurvey of COVID-19 provides a better estimation of people who have developed antibodies against the infection. Undertaking such a serosurvey in certain districts of India which are densely populated with prominent tribes can provide valuable information regarding seropravelance of SARS-CoV-2 antibodies among such indigenous populations. In this context, two rounds of population-based, cross-sectional serosurveys for SARS-CoV-2 IgG antibody were carried out in Jharkhand, a tribal-dominated State of India, to compare the seroprevalence of SARS-CoV-2 infection and to determine the associated demographic risk factors. Methods: The surveys were carried out in June 2020 and February 2021 in ten districts of the State of Jharkhand. Blood samples were collected from the residents of the selected districts by random sampling and tested for anti-SARS-CoV-2 antibodies using an automated chemiluminescence immunoassay platform. A total of 4761 and 3855 eligible participants were included in round 1 and round 2, respectively. Results: The age- and gender-standardized seroprevalence for COVID-19 during round 1 was 0.54 per cent (0.36-0.80) that increased to 41.69 per cent (40.16-43.22) during round 2 with a gap of eight months in between. The seropositivity among male and female participants was 0.73 and 0.45 per cent, respectively, during the first round and 51.35 and 33.70 per cent, respectively, during the second round. During the first round, 17.37 per cent of the participants were tribal with seropositivity of 0.24 per cent (0.02-0.87), and during the second round, 21.14 per cent were tribal with seropositivity of 39.14 per cent (35.77-42.59). Compared to tribal group, non-tribal participants had an adjusted odds of 1.24 (95% confidence interval=1.04-1.48) for SARS-CoV-2 seropositivity. Interpretation & conclusions: COVID-19 seroprevalence was found to be low during the first round (0.54%) of the survey, possibly due to the travel restrictions during lockdown better adherence to social distancing and wearing of face masks among the people. Understanding the dynamics of SARS-CoV-2 transmission and the susceptibility to infection at the individual as well as community level will inform decision and help policy makers to design and implement effective public health strategies to mitigate the pandemic in this State.

iTRAQ-based proteomic analysis of differentially expressed proteins in sera of seronegative and seropositive rheumatoid arthritis patients.

OBJECTIVE: The diagnosis of seronegative rheumatoid arthritis (SNRA) is often difficult due to the unavailability of reliable laboratory markers. The aim of this study was to identify differentially expressed proteins in sera of SNRA, seropositive RA (SPRA), and healthy donors (HD). METHODS: A total of 32 seropositive RA patients, 32 SNRA patients, and 35 HD were enrolled in our study. Differentially expressed proteins between 3 groups were identified via isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis, and an ELISA test was used for the validation test. Correlation analysis was conducted by GraphPad Prism. RESULTS: Using iTRAQ quantitative proteomics, we identified 14 proteins were significantly different between SPRA and SNRA, including 4 upregulated proteins and 10 downregulated proteins. Four differentially expressed proteins were validated by ELISA test, and the results showed that SAA1 protein was significantly higher in SPRA and SNRA patients compared with HD, and PSME1 was elevated in SPRA patients. What's more, SAA1 was increased in the anti-CCP or RF high-level group in RA patients, and PSME1 was increased in the RF high-level group. Alternatively, SAA1 was positively correlated with inflammation indicators in RA patients, while PSME1 showed no correlation with inflammation indicators. CONCLUSIONS: iTRAQ proteomic approaches revealed variations in serum protein composition among SPRA patients, SNRA patients, and HD and provided new idea for advanced diagnostic methods and precision treatment of RA.

Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy.

Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6-8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.

Effect of active anticancer therapy on serologic response to SARS-CoV-2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma.

OBJECTIVES: To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma. METHODS: Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma. RESULTS: Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune-related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity. CONCLUSIONS: Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

Comorbidities at diagnosis of rheumatoid arthritis: a population-based case-control study.

OBJECTIVES: Comorbidities contribute to the morbidity and mortality in RA, and are thus important to capture and treat early. In contrast to the well-studied comorbidity risks in established RA, less is known about the comorbidity pattern up until diagnosis of RA. We therefore compared whether the occurrence of defined conditions, and the overall comorbidity burden at RA diagnosis, is different from that in the general population, and if it differs between seropositive and seronegative RA. METHODS: Using Swedish national clinical and demographic registers, we identified new-onset RA patients (n = 11 086), and matched (1:5) to general population controls (n = 54 813). Comorbidities prior to RA diagnosis were identified in the Patient and Prescribed Drug Registers, and compared using logistic regression. RESULTS: At diagnosis of RA, respiratory (odds ratio (OR) = 1.58, 95% CI: 1.44, 1.74), endocrine (OR = 1.39, 95% CI: 1.31, 1.47) and certain neurological diseases (OR = 1.73, 95% CI: 1.59, 1.89) were more common in RA vs controls, with a similar pattern in seropositive and seronegative RA. In contrast, psychiatric disorders (OR = 0.87, 95% CI: 0.82, 0.92) and malignancies (OR = 0.88, 95% CI: 0.79, 0.97) were less commonly diagnosed in RA vs controls. The comorbidity burden was slightly higher in RA patients compared with controls (P <0.0001). CONCLUSION: We found several differences in comorbidity prevalence between patients with new-onset seropositive and seronegative RA compared with matched controls from the general population. These findings are important both for our understanding of the evolvement of comorbidities in established RA and for early detection of these conditions.

Impact of MBL-2 coding region polymorphism on modulation of HAND and HIV-1 acquisition.

BACKGROUND: Mannose-binding lectin 2 (MBL2) gene has a significant role in the essential protective mechanism of the body. Variations reported in the genetic makeup of this gene influence the circulating MBL levels that could lead to the vulnerability to various viral infections including HIV. Hence, we assessed the MBL2 coding region (52A/D, 54A/B, and 57A/C) variations in HIV-associated neurocognitive disorders (HAND). METHOD: In this proposed study, 208 HIV seropositive individuals were included, 104 were on ART undergone for IHDS evaluation (44 HAND+60 without HAND), and 104 HIV seropositive individuals naïve to ART, and 130 unrelated HIV uninfected individuals. PCR-RFLP was used to genotype the MBL2 coding region polymorphism (52A/D, 54A/B and 57A/C). RESULTS: MBL-2 57AC genotype was associated with risk of HAND severity (OR = 4.69, P = 0.0009). MBL-2 57AC and 57C alleles were associated with susceptibility to HAND (OR = 3.14, P = 0.003). Furthermore, the MBL-2 57AC genotype and 57C allele were found to be significantly linked with the susceptibility to HIV disease severity. (OR = 6.34, P = 0.001; 16.82% vs. 3.46%, OR = 5.64, P = 0.001). Haplotype ACA was significantly linked with susceptibility to HAND and its severity (OR = 3.23, P = 0.004, 26.1%-8.1%, OR = 4.70, P = 0.0024), similarly, haplotype ACA was linked with the acquisition of HIV-1 (OR = 4.26, P = 0.005). MBL-2 57AC genotype in presence of tobacco showed a significantly higher risk for HIV disease severity (48.0% vs. 12.5%, OR = 7.00, P = 0.035). Alcohol-taking HIV seropositive individuals on ART showed a greater MBL-2 57AC genotype than with alcohol-taking naïve to ART (32.3% vs. 15.4%, OR = 2.75, P = 0.40). CONCLUSION: MBL-2 57AC genotype and haplotype ACA were associated with the modulation of HAND. Individuals with haplotype ACA were at higher risk of HIV-1 acquisition.

Serum antibody response to BNT162b2 after natural SARS-CoV-2 infection.

BACKGROUND: There is preliminary evidence that individuals with previous SARS-CoV-2 infections exhibit a more pronounced antibody response. However, these assumptions have not yet been supported by data obtained through various CE-marked tests. This study aimed to close this gap. METHODS: Sixty-nine seronegatives and 12 individuals post-SARS-CoV-2 infection (tested by CE-labelled Roche NC immunoassay or PCR-confirmed assay) were included 21 ± 1 days after receiving the first dose of the Pfizer/BioNTech BNT162b2 vaccine. Antibody response to viral spike protein (S) was assessed by CE-labelled Roche S and DiaSorin S1/S2 assays and by a surrogate virus neutralization test (sVNT). RESULTS: After a single dose of BNT162b2, individuals after natural SARS-CoV-2 infection presented with markedly higher anti-S levels than naïve individuals (Roche S: 9078.5 BAU/mL [5267.0-24 298.5] vs 79.6 [24.7-142.3]; and DiaSorin S1/S2: 1465.0 AU/mL [631.0-5365.0] vs 63.7 [47.8-87.5]) and showed all the maximum observed inhibition activity in the sVNT (98%), without overlaps between groups. There was a trend for higher responses in those with a more distant infection, although not statistically significant. The relative antibody increase after dose 2 was significantly higher among naïve individuals (25-fold), but antibody levels remained below that of seropositives. CONCLUSIONS: Compared with naïve individuals, seropositives after natural SARS-CoV-2 infection presented with a substantially higher antibody response already after dose 1 of BNT162b2, as measured by two CE-marked in vitro diagnostic tests and a sVNT. These results should stimulate discussion and research on whether individuals after previous SARS-CoV-2 infection would benefit from a two-part vaccination schedule or whether these currently much-needed second doses could be saved.

Evaluation of brain and spinal cord lesion distribution criteria at disease onset in distinguishing NMOSD from MS and MOG antibody-associated disorder.

OBJECTIVE: To validate the recently proposed imaging criteria in distinguishing aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD) at disease onset in a Chinese population. METHODS: We enrolled 241 patients in this retrospective study, including 143 AQP4-ab-seropositive NMOSD, 73 MS, and 25 MOG-AD. Cacciaguerra's criteria were described as fulfillment of at least 2/5 conditions including the absence of the combined juxtacortical/cortical lesions, the presence of longitudinal extensive transverse myelitis (LETM) lesions, the presence of periependymal-lateral ventricles lesions, the absence of Dawson's fingers lesions, and the absence of periventricular lesions. RESULTS: Fulfillment of at least 3/5 conditions was able to differentiate NMOSD from MS with a good diagnostic performance (accuracy = 0.92, sensitivity = 0.91, specificity = 0.93), yet failed to differentiate NMOSD from MOG-AD. LETM lesions showed the highest accuracy (0.78), sensitivity (0.70), and specificity (0.97) for NMSOD. CONCLUSION: Our research suggested the utility of Cacciaguerra's criteria in a Chinese population at disease onset. A better diagnostic performance in NMOSD could be attained with at least 3/5 conditions fulfilled. Yet their utility in distinguishing NMOSD from MOG-AD was limited.

Anti-cN1A antibodies do not correlate with specific clinical, electromyographic, or pathological findings in sporadic inclusion body myositis.

BACKGROUND: Anti-cytosolic 5'-nucleotidase 1A (cN1A) antibodies are commonly detected in patients with sporadic inclusion body myositis (sIBM). However, their pathogenic role has not been established. Moreover, efforts toward identifying sIBM distinct clinicopathologic characteristics associated with these antibodies have yielded conflicting results. METHODS: We first searched for patients, seen in our clinics, tested for anti-cN1A antibodies between December 2015 and December 2019. We identified 92 patients who were diagnosed with sIBM, according to the 2011 ENMC or Griggs et al criteria. Thereafter, we reviewed and compared the clinical and investigational findings of these patients in relation to their antibody status. RESULTS: Anti-cN1A antibodies were present in 47/92 (51%) patients with sIBM. Comparison of seropositive and seronegative cohorts yielded no significant difference in clinical features, including facial weakness, oropharyngeal and respiratory involvement, or disease severity. The antibody titer did not correlate with the clinical phenotype, CK value, or presence of myotonic discharges on EMG. Anti-cN1A antibody positive patients appeared to have more frequent auto-aggressive inflammation on muscle biopsy but not as an isolated myopathological feature. CONCLUSIONS: Our study showed that anti-cN1A antibody positive and negative sIBM patients have similar clinical features and disease severity. Anti-cN1A antibodies in our sIBM cohort did not correlate with any studied clinical or laboratory parameter and, therefore, were of limited value in the patient's assessment.

Brucellosis screening and follow-up of seropositive asymptomatic subjects among household members of shepherds in China.

To measure the seroprevalence of high-exposure populations in brucellosis endemic areas and report the outcome and duration of seropositive asymptomatic subjects, we screened 595 family members of shepherds in Jilin Province, China and then followed up 15 seropositive asymptomatic subjects for 18 months. We found that the seropositive rate of 15.5%. Nearly half of seropositive asymptomatic subjects (7/15) developed into brucellosis in the short term; others were still seropositive asymptomatic or had decreased SAT titer in a longer time.