Gut microbiome-immune interactions and their role in rheumatoid arthritis development.

Objective: The primary objective is to study the impact of gut microbiota and their interactions with diverse immunological markers on the development of rheumatoid arthritis. Methods: This study was performed in Astana, Kazakhstan, and included 77 Kazakh female patients older than 18 years, who met the American College of Rheumatology 2010 classification criteria for rheumatoid arthritis (RA), and 113 healthy controls. The DNA was extracted from fecal samples obtained from all study participants for subsequent sequencing at the 16S rRNA gene V1-V3 locus, facilitating the analysis of the gut microbiome. The Multiplex immunoassay was employed to measure the concentrations of inflammatory cytokines, chemokines, and immunoglobulins in both fecal and plasma samples. Results: Our taxonomic analysis revealed significant differences in the composition of the gut microbiota between the healthy control cohort and the cohort with rheumatoid arthritis RA. Alpha diversity was significantly lower in the RA group. Lachnospiraceae were the most abundant taxon and found to be crucial, showing correlations with immunological markers such as IL5. Additionally, Lachnospiraceae and Oscillospiraceae exhibited the most predictable power and distinguished the composition of both study groups. Conclusion: Our study identifies key differences in the gut microbiome of RA patients, revealing distinct microbial patterns and specific taxa abundance. We highlight potential biomarkers in immunological and bacterial pathways, offering insights into RA development and indicating possibilities for personalized treatment.

Oral Microbial Signature of Rheumatoid Arthritis in Female Patients.

This study aimed to identify the oral microbial signature of Kazakh female rheumatoid arthritis (RA) patients. A total of 75 female patients who met the American College of Rheumatology 2010 classification criteria for RA and 114 healthy volunteers were included in the study. Amplicons of the 16S rRNA gene were sequenced to analyze the microbial composition. We identified significant differences in bacterial diversity and abundance between the RA and control groups, as measured by Shannon (p value = 0.0205) and Simpson (p value = 0.00152) indices. The oral samples from RA patients had higher bacterial diversity than those from non-RA volunteers. The RA samples had a higher relative abundance of Prevotellaceae and Leptotrichiaceae, but a lower content of butyrate and propionate-producing bacteria compared to the control group. The samples from patients in remission had a higher abundance of Treponema sp. and Absconditabacteriales (SR1), whereas those with low disease activity had higher levels of Porphyromonas and those with high RA activity had higher levels of Staphylococcus. A positive correlation was found between the taxa Prevotella_9 and serum levels of antibodies to cyclic citrullinated peptide (ACPA) and rheumatoid factor (RF). The predicted functional pattern of the ACPA+/RF- and ACPA+/RF+ seropositive groups was characterized by increased ascorbate metabolism, degradation of glycosaminoglycans, and reduced biodegradation of xenobiotics. These findings suggest that the functional pattern of the microflora should be considered when selecting a therapeutic strategy for RA in order to provide a personalized approach.

Association Study of Anticitrullinated Peptide Antibody Status with Clinical Manifestations and SNPs in Patients Affected with Rheumatoid Arthritis: A Pilot Study.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia. Methods: Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin. Conclusion: Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.

Effects of air temperature on the number of ambulance calls for asthma during cold season in Nur-Sultan- the second coldest capital in the world.

Deleterious effect of cold on overall mortality is well-established. We studied associations between the air temperature and the number f ambulance calls for asthma in Nur-Sultan, Kazakhstan - the second coldest capital in the world. Daily counts of ambulance calls for asthma in Nur-Sultan for the cold seasons (October-March) 2006-2010 were obtained from the Municipal Ambulance Station. Associations between the number of calls and mean and minimum apparent temperatures (average for lags 0-15) were studied using first-order Poisson auto-regression models controlling for wind speed and effects of month, year, weekends and holidays. Altogether, there were 7373 ambulance calls for asthma during the study period. An inverse association between minimum apparent temperature and the number of calls was observed for the age-group 60 years and older. A decrease of the minimum apparent temperature by 1°C was associated with an increase in the number of calls by 1.7% (95% CI: 0.1%-3.3%) across the whole temperature spectrum. No associations in other age groups were found. Our results suggest an inverse association between the average 15-day lag minimum apparent temperature and the number of ambulance calls during the cold season in Nur-Sultan, but this is limited to the oldest age-group.

Cost-effectiveness of Oral Protease Inhibitors Co-administration versus Pegylated Interferon-Α2b and Ribavirin Only for the Patients with Hepatitis C Genotype 1 in Kazakhstan Health Care Settings.

BACKGROUND: The triple therapy including peginterferon, ribavirin and protease inhibitors was more effective compared to the combination of only peginterferon and ribavirin. This study aimed to assess the cost-effectiveness of triple treatment in either treatment-naïve and treatment-experienced patients in Kazakhstan. METHODS: A Markov model was created to assess long-term clinical advantages and the cost-effectiveness of the triple therapy from Kazakhstan payer perspective. Health state transition probabilities, pharmaceutical and other costs (according to the price in 2015), and utility rate were acquired from the published studies and publicly available sources. All used costs and benefits were discounted at 5% per year. RESULTS: Despite treatment background, the patients, receiving boceprevir and telaprevir, were estimated to experience less serious liver-disease complications, more life-years, and more QALYs compared to the patients having standard of care. For treatment-experienced group, boceprevir and telaprevir were dominant, with more QALYs. For all the groups of patients, incremental costs per QALY gained were between USD14995 and USD18075. The total average cost of boceprevir is slightly more costly than a standard duration of treatment with telaprevir, and so is the average cost per SVR. Extensive sensitivity analyses verified robust model results. CONCLUSION: The inclusion of protease inhibitors to standard management for the therapy of patients with genotype 1 chronic HCV infection in Kazakhstan is predicted to be cost-effective using a typically applied willingness to pay threshold of USD37805 (3 times GDP per capita).