Faculty Bibliography

Objective: To characterize the gut microbiota and host gene interactions in Reactive Arthritis (ReA) and postinfectious SpA. Methods: 32 patients with ReA and 32 controls with preceding Gastrointestinal (GI) and/or Genitourinary (GU) infections that did not develop arthritiswere prospectively recruited in Guatemala, a highly prevalent geographic region for this disease. Clinical variables, HLA status and 16S ribosomal RNA gene sequencing of intestinal microbiota were analysed. Results: Subjects with ReA showed no significant differences from controls in gut bacterial richness, alpha or beta diversity. However there was a higher abundance of Erwinia and Pseudomonas, and increased prevalence of typical enteropathogens associated with ReA. In Fact, at least one enteropathogen was present in 71.9% of ReA subjects vs 46.8% of controls (p<0.05). Subjects with ultrasound evidence of enthesitiswere enriched with Campylobacter,while subjects with Uveitis and radiographic sacroiliitis were enriched with Erwinia and unclassified Ruminococcaceae, respectively. Both were enriched in Dialister (log LDA>2). Host genetics, particularly HLA-A24 were associated with differences in gut microbiota diversity irrespective of disease status. We identified several co-occurring taxa that were also predictive of HLA-A24 status, including Ruminococcaceae-Rikenellaceae-Coriobacteriacea and Prevotellaceaeunclassified Sphingobacteriales-Elusimicrobiaceae. Conclusion: This is the first culture-independent study characterizing the gut microbial community of ReA. Although bacterial factors correlated with disease presence and clinical features of ReA, host genetics also appeared to be a major independent driver of intestinal community composition. Understanding of these gut microbiota host-genetic relationships may further clarify the pathogenesis of ReA and related Spondyloarthritis

Objective: To identify potential risk factors for the development of Reactive Arthritis (ReA) among Guatemalan patients with a known history of being infected with gastrointestinal (GI), genitourinary (GU), or sexually transmitted pathogens. A prospective study was performed to examine clinical, environmental, and genetic risk factors for the development of ReA. Methods: Patients were enrolled from July to October 2014. Cases and controls were recruited in the same time window. Cases were ascertained from 2 rheumatology clinics in Guatemala City: Asociacion Guatemalteca Anti Enfermedades Reumaticas (AGAR) and AGK: Private Clinic. ReAwas defined as inflammatory arthritis following a gastrointestinal (GI) or genitourinary infection (GU) and meeting the ASAS peripheral SpA criteria. Subjects had a preceding GI or GU infection 3-6 months before enrolment. A standardized questionnaire ascertained infection details, family history, medication, medical comorbidities, smoking status and literacy. Subjects completed a standardized joint and enthesis examination, radiographs of the Sacroiliac (SI) joints interpreted by a trained radiologist and ultrasound (USG) of the Achilles tendons. Results: 32 patients with ReA and 32 controls were enrolled.Mean age was 39 and 36 respectively. The majority of patients were female (81% and 63% (Figure presented) respectively). None of the controls had swollen or tender joints or entheses. History of Uveitis was present in 60%. The most frequent tender joint: right SI joint (81%). (see figure 1). The most common finding on SI joint Xray: bilateral sacroiliitis 45%. Enthesitis was noted on Achilles tendon ultrasound in 44% cases. All ReA patients had peripheral arthritis and 91% had back pain. Only 2 subjects from each group were found to carry an HLA-B27 allele. The most frequent HLA-A allele was HLA-A2 in both patients 44% and controls 63%. Serum Cathepsin K(ng/mL) levels were elevated in patients with ReA compared to controls (2.70 vs 2.17 p=0.028). All patients completed a follow up survey at 2 years (in person or by phone). 47% of patients had continued symptoms. Uveitis resolved in all but one of the patients. Conclusion: We report the results of a study examining the epidemiology of ReA in Guatemala. As expected, SpA characteristics were common: Achilles Enthesitis (67% on exam, 44% on USG). Strengths of this study: First, 81% were female, previous studies have reported ReA as a male-predominant disease, but as in Ankylosing Spondylitis (AS) women comprise a larger proportion of patients than previously recognized when newer definitions are used. This is the first study to examine potential risk factors for ReA, including serum biomarkers. Finally, this is one of the few studies to follow patients for persistence or resolution of symptoms at 2 years

OBJECTIVE: Reactive arthritis (ReA) is an inflammatory disorder occurring several weeks after gastrointestinal or genitourinary infections. HLA-B27 positivity is considered a risk factor, though not necessarily predictive of disease incidence. Among non-genetic factors, the intestinal microbiome may play a role in disease susceptibility. The objective of this study was to characterize the gut microbiota and host gene interactions in ReA and post-infectious spondyloarthritis. METHODS: Adult peripheral spondyloarthritis and control subjects with preceding infections that did not develop arthritis were prospectively recruited from a highly prevalent geographic region. Clinical variables, HLA status, and 16S rRNA gene sequencing of intestinal microbiota were analyzed. RESULTS: ReA subjects showed no significant differences from controls in gut bacterial richness or diversity. However, there was a significantly higher abundance of Erwinia and Pseudomonas, and increased prevalence of typical enteropathogens associated with ReA. Subjects with ultrasound evidence of enthesitis were enriched in Campylobacter, while subjects with uveitis and radiographic sacroiliitis were respectively enriched in Erwinia and unclassified Ruminococcaceae, and both enriched in Dialister. Host genetics, particularly HLA-A24, were associated with differences in gut microbiota diversity irrespective of disease status. We determined several co-occurring taxa that were also predictive of HLA-A24 status. CONCLUSION: This is the first culture-independent study characterizing the gut microbial community of post-infectious arthritis. Although bacterial factors correlated with disease presence and clinical features of ReA, host genetics also appeared to be a major independent driver of intestinal community composition. Understanding of these gut microbiota host-genetic relationships may further clarify the pathogenesis of post-infectious spondyloarthropathies.

The objective of the study is to determine the risk factors for the development of reactive arthritis (ReA) and examine the factors associated with the persistence of symptoms. Patients with a new diagnosis of ReA and controls with a gastrointestinal (GI), urogenital, or sexually transmitted infection in the 3-6 months prior to study entry were prospectively enrolled in Guatemala City. ReA patients fulfilled the Assessment in Spondyloarthritis International Society criteria for peripheral spondyloarthropathy (SpA). Patients underwent history, examination, Achilles tendon ultrasound, and blood draw. Human leukocyte antigen (HLA) type and serum biomarkers were measured. t tests and nonparametric equivalents were used to examine the association of clinical, laboratory, and imaging factors with ReA. Patients were contacted 2 years later to assess for persistence of symptoms. Study subjects included patients with ReA (N = 32) and controls (N = 32). ReA patients were most frequently infected in April whereas controls were most frequently infected in August. Two ReA patients and two controls were HLA-B27-positive. Serum cathepsin K and C-reactive protein were higher in ReA patients compared to controls (p = 0.03 for both), while total cholesterol and low-density lipoprotein were lower (p = 0.008 and 0.045, respectively). Among those with ReA, 15 (47%) patients had continued symptoms at 2 years. These patients had a lower matrix metalloproteinase-3 level at diagnosis than patients for whom ReA resolved (p = 0.004). HLA-B27 was not associated with development of ReA in Guatemala; however, the month of infection was associated with ReA. The most striking finding was the persistence of arthritis at 2 years in nearly half of the patients.

The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.

Background/UNASSIGNED:To evaluate demographics, family history, and previous medication use at enrollment in a subset of psoriasis patients with self-reported psoriatic arthritis (PsA) enrolled in Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods/UNASSIGNED: = 12,090). Results/UNASSIGNED: < 0.001). Overall, 17.5% of psoriasis patients self-reporting PsA had a family history of PsA, 29.8% had used systemic steroids, 39.5% had used nonsteroidal anti-inflammatory drugs, and 83.5% had used biologics. Conclusions/UNASSIGNED:Demographics, family history, and previous medication use were generally comparable between "PsA established by a HCP" patients and psoriasis patients self-reporting PsA in the PSOLAR registry, but there were statistical differences compared with the psoriasis only group regarding the prevalence of certain comorbidities (CVD, psychiatric illness, and IBD). These analyses provide important data regarding characteristics of psoriasis patients with self-reported PsA in PSOLAR. Trial registration/UNASSIGNED:NCT00508547.

Microbes have coevolved with their human hosts for millions of years and are vital to their normal development and homoeostasis. It is now clear that there is direct and indirect cross talk between the microbiome and host immune responses. However, the exact mechanisms for this microbial influence in disease pathogenesis remain elusive and are now a major research focus.