The faecal microbiota is distinct in HLA-B27+ ankylosing spondylitis patients versus HLA-B27+ healthy controls.

OBJECTIVES: Spondyloarthritis (SpA) results from the interplay between genetic and environmental factors. An emerging modifiable factor is the human intestinal microbiota, which multiple studies in children and adults have shown to be abnormal in SpA patients, including enthesitis related arthritis and ankylosing spondylitis (AS). However, HLA-B27 itself appears to impact the contents of the microbiota and is more common in SpA patients versus controls, thus serving as a confounding factor in most comparative studies. METHODS: This was a cross-sectional study that evaluated the contents of the faecal microbiota among 29 patients with HLA-B27+ AS and 43 healthy adults who underwent 16S sequencing and genotyping as part of the TwinsUK Programme. RESULTS: HLA-B27 positive+ patients and healthy controls demonstrated substantial clustering based upon diagnosis. Decreased richness was observed among the AS patients, although measures of evenness were similar. After correction for multiple comparisons, several taxa - including Faecalibacterium prausnitzii and Coprococcus - were elevated in AS patients compared to controls, even when restricted to female subjects, while Bacteroides fragilis, Ruminococcus, and Akkermansia muciniphila were depleted in AS patients. CONCLUSIONS: Consistent with some previous studies, our study demonstrates in patients with AS associations with Coprococcus, Bacteroides, and Ruminococcus. Other findings, including increased Faecalibacterium, are inconsistent with previous studies and thus potentially underscore the necessity of evaluating HLA-B27 positive controls in studies evaluating the impact of the intestinal microbiota on SpA.

Correction: Stoll et al. Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients. Children 2022, 9, 569.

The authors wish to make the following correction to this paper [...].

Impact of HLA-B27 and Disease Status on the Gut Microbiome of the Offspring of Ankylosing Spondylitis Patients.

Multiple studies have shown the microbiota to be abnormal in patients with spondyloarthritis (SpA). The purpose of this study was to explore the genetic contributions of these microbiota abnormalities. We analyzed the impact of HLA-B27 on the microbiota of children at risk for SpA and compared the microbiota of HLA-B27+ pediatric offspring of ankylosing spondylitis (AS) patients with that of HLA-B27+ children with SpA. Human DNA was obtained from the offspring for determination of HLA-B27 status and polygenic risk score (PRS). Fecal specimens were collected from both groups for sequencing of the V4 region of the 16S ribosomal RNA gene. Among the offspring of AS patients, there was slight clustering by HLA-B27 status. After adjusting for multiple comparisons, five operational taxonomic units (OTUs) representing three unique taxa distinguished the HLA-B27+ from negative children: Blautia and Coprococcus were lower in the HLA-B27+ offspring, while Faecalibacterium prausnitzii was higher. HLA-B27+ offspring without arthritis were compared to children with treatment-naïve HLA-B27+ SpA. After adjustments, clustering by diagnosis was present. A total of 21 OTUs were significantly associated with diagnosis state, including Bacteroides (higher in SpA patients) and F. prausnitzii (higher in controls). Thus, our data confirmed associations with B. fragilis and F. prausnitzii with juvenile SpA, and also suggest that the mechanism by which HLA-B27 is associated with SpA may not involve alterations of the microbiota.

Cardiovascular Risk Scores in Axial Spondyloarthritis Versus the General Population: A Cross-sectional Study.

OBJECTIVE: Cardiovascular (CV) morbidity and mortality are increased in axial spondyloarthritis (axSpA).We conducted a cross-sectional study evaluating the 10-year atherosclerotic cardiovascular disease (ASCVD) risk in axSpA compared to the general US population. METHODS: We included 211 adults, 40-75 years old with ankylosing spondylitis (AS) or nonradiographic axSpA from 2 sites, who had available data on comorbidities, medication use, blood pressure measures, and laboratory cholesterol values. General population comparators from the 2009-2014 National Health and Examination Survey (NHANES) cycles were matched 4:1 to subjects, on age, sex, and race. We estimated the prevalence ratio for a 10-year ASCVD risk score ≥ 7.5% comparing axSpA and matched NHANES comparators using conditional Poisson regression. RESULTS: Overall, subjects were 53.9 ± 11.2 years old, 69% were male, and 74% were White. The mean 10-year ASCVD risk score was 6.7 ± 6.9% for those with axSpA, and 9.0 ± 10.5% for NHANES comparators. Compared to those with axSpA, the prevalence of current smoking and diabetes was higher among NHANES comparators. The estimated prevalence ratio for a 10-year ASCVD risk score ≥ 7.5% comparing those with axSpA and their age-, sex-, and race-matched comparators was 0.96 (95% CI 0.74-1.24). CONCLUSION: The prevalence of a 10-year ASCVD risk score ≥ 7.5% was not significantly different comparing axSpA patients and those drawn from the general population who were similar in terms of age, sex, and race. Future studies should focus on improved CV risk prediction in axSpA, because underestimation by a general population risk score may potentially explain these results.

Retrospective Chart Review of Intravenous Valproate Sodium as a Preventive Treatment for Patients With Chronic Migraine.

OBJECTIVE: This is a small pilot study to evaluate the effectiveness of an intravenous (IV) valproate sodium therapy protocol for migraine prevention in a population of patients with chronic migraine refractory to multiple preventive medications. BACKGROUND: Valproate sodium is an anti-epileptic and mood stabilizer that has been shown to prevent migraine when used daily in oral form. The specific mechanism of action in migraine is unknown, but it may be related to suppressing inflammation and increasing brain Gamma-aminobutyric acid levels. It also may relate to its ability to suppress cortical spreading depression. Multiple studies have suggested that valproic acid and its derivatives may inhibit Calcitonin gene-related peptide. In the present work, we undertook a small pilot study to evaluate the effectiveness of an IV valproate sodium therapy for migraine prevention in a population of patients with chronic migraine refractory to multiple preventive medications. METHODS: Fourteen adult patients with chronic migraine were admitted for a 4-day course of IV valproate sodium. Patients received 250 mg of valproate sodium over a standard infusion time of 60 minutes every 8 hours. Most patients received 9 doses over the 4-day course of treatment. One patient had to discontinue after 1 dose of 250-mg valproate sodium, as this patient experienced an increase in his previous symptoms of nausea, vomiting, and vertigo with his first dose. To avoid positive selection bias, we evaluated the first admission for valproate IV therapy in patients with multiple admissions; there was 1 patient with 2 admissions and 1 with 3 admissions for IV valproate sodium. Of note - all admission outcomes for these patients were similar. Headache diaries were reviewed from 1 month before, during, and approximately 2 months after their admission. STATISTICAL ANALYSES: Due to the observational nature of the study and small sample size, we did not think that quantitative statistical analysis would add more meaning to this pilot study. Formal quantitative statistical analysis was not performed in this study and descriptive statistical analysis was used due to this being a pilot proof of concept study. Physician clinical judgment in combination with patient reports were used to assign a dichotomous conclusion on clinical improvement for each patient. In the future, we plan to create a larger study, including additional treatment groups for control, such as IV Dihydroergotamine or IV Chlorpromazine, in order to quantify improvement of symptoms. RESULTS: A total of 9 out of 13 (69%) patients had an improvement in their headache post-admission and reported a reduction in headache frequency, intensity, and/or use of acute medications 4-6 weeks following their admissions. A total of 5 out of 13 (38%) patients also reported an improvement in headache intensity during the 4-day period of inpatient admission. The other 8 out of 13 (62%) patients reported stable headache pattern. One patient had feelings of restlessness, which improved with prolongation of infusion time to 120 minutes. CONCLUSION: These results indicate that this repetitive dosing valproate sodium protocol is a safe and well-tolerated intervention for the treatment of chronic migraine resistant to oral medications. Given the promising outcomes on patient headache improvement with this small pilot study, studies to confirm this benefit in a larger cohort of chronic migraine patients are warranted, preferable with the addition of a blinded control group for comparison.