ABSTRACT
BACKGROUND: The oral microbiota has been implicated in the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. This study tested for associations between oral health, microbial communities and juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional exploratory study of subjects aged 10-18 years with oligoarticular, extended oligoarticular and polyarticular JIA was conducted. Control groups included pediatric dental clinic patients and healthy volunteers. The primary aim was to test for an association between dental health indices and JIA; the secondary aim was to characterize the microbial profile of supragingival plaque using 16S rRNA gene sequencing. RESULTS: The study included 85 patients with JIA, 62 dental patients and 11 healthy child controls. JIA patients overall had significantly more gingival inflammation compared to dental patients, as evidenced by bleeding on probing of the gingiva, the most specific sign of active inflammation (p = 0.02). Overall, however, there was a trend towards better dental hygiene in the JIA patients compared to dental patients, based on indices for plaque, decay, and periodontitis. In the JIA patients, plaque microbiota analysis revealed bacteria belonging to genera Haemophilus or Kingella elevated, and Corynebacterium underrepresented. In poly JIA, bacteria belonging to the genus Porphyromonas was overrepresented and Prevotella was underrepresented. CONCLUSION: Increased gingival inflammation in JIA was independent of general oral health, and thus cannot be attributed to poor dental hygiene secondary to disability. The variation of microbial profile in JIA patients could indicate a possible link between gingivitis and synovial inflammation.
Subject(s)
Arthritis, Juvenile/etiology , Dental Plaque/complications , Microbiota , Oral Health , Adolescent , Arthritis, Juvenile/microbiology , Case-Control Studies , Child , Cross-Sectional Studies , Dental Plaque/microbiology , Female , Humans , Male , Microbiota/genetics , Mouth/microbiology , Periodontitis/complications , Periodontitis/microbiology , RNA, Ribosomal, 16S/geneticsABSTRACT
Objectives: To evaluate the prevalence of special diet adoption in juvenile idiopathic arthritis (JIA) and parental perceptions of efficacy. Design: An online survey was distributed over a year to nearly 20,000 individuals. Results: Responses from 261 parents of patients with JIA were received. One of three (n = 79) had tried special diets, including gluten-free (66%), anti-inflammatory (41%), and lactose-free (25%). Overall, >50% of 79 parents reported that patients had improved pain or joint swelling. Conclusions: Special diets have been trialed by a third of the patients, with over half reporting symptom improvement. A prospective, controlled trial is warranted to test the efficacy of a dietary approach to JIA.
Subject(s)
Arthritis, Juvenile/diet therapy , Feeding Behavior , Parents , Patient Satisfaction , Adolescent , Adult , Anti-Inflammatory Agents/administration & dosage , Arthritis, Juvenile/complications , Child , Child, Preschool , Diet, Gluten-Free , Edema/prevention & control , Female , Foods, Specialized , Glutens/adverse effects , Humans , Infant , Lactose/adverse effects , Male , Pain/prevention & control , Perception , Surveys and Questionnaires , Young AdultABSTRACT
Systemic juvenile idiopathic arthritis (SJIA) is a disease marked with arthritis and several features of systemic inflammation including fevers, rashes, hepatosplenomegaly, lymphadenopathy, and serositis. The presentation can be variable and arthritis can be a later feature. Macrophage activation syndrome can be a life-threatening complication of this illness and requires early recognition and prompt therapy. Advancements in understanding the biology of SJIA have led to the development of cytokine-targeted therapies, mainly interleukin-1 (IL-1) and IL-6 inhibitors that have significantly improved outcomes. In this review, we provide an update on the advances in the understanding of SJIA biology and also the therapeutic options.
ABSTRACT
The NLRP3 inflammasome is an intracellular innate immune sensor that is expressed in immune cells, including monocytes and macrophages. Activation of the NLRP3 inflammasome leads to IL-1ß secretion. Gain-of-function mutations of NLRP3 result in abnormal activation of the NLRP3 inflammasome, and cause the autosomal dominant systemic autoinflammatory disease spectrum, termed cryopyrin-associated periodic syndromes (CAPS). Here, we show that a missense mutation, p.Arg918Gln (c.2753G > A), of NLRP3 causes autosomal-dominant sensorineural hearing loss in two unrelated families. In family LMG446, hearing loss is accompanied by autoinflammatory signs and symptoms without serologic evidence of inflammation as part of an atypical CAPS phenotype and was reversed or improved by IL-1ß blockade therapy. In family LMG113, hearing loss segregates without any other target-organ manifestations of CAPS. This observation led us to explore the possibility that resident macrophage/monocyte-like cells in the cochlea can mediate local autoinflammation via activation of the NLRP3 inflammasome. The NLRP3 inflammasome can indeed be activated in resident macrophage/monocyte-like cells in the mouse cochlea, resulting in secretion of IL-1ß. This pathway could underlie treatable sensorineural hearing loss in DFNA34, CAPS, and possibly in a wide variety of hearing-loss disorders, such as sudden sensorineural hearing loss and Meniere's disease that are elicited by pathogens and processes that stimulate innate immune responses within the cochlea.
Subject(s)
Hearing Loss, Sensorineural/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Adult , Animals , Base Sequence , Carrier Proteins/metabolism , Cochlea/metabolism , Cryopyrin-Associated Periodic Syndromes/genetics , Cryopyrin-Associated Periodic Syndromes/metabolism , Deafness/genetics , Family , Female , Hearing Loss , Hearing Loss, Sensorineural/metabolism , Humans , Inflammasomes/metabolism , Inflammation/metabolism , Interleukin 1 Receptor Antagonist Protein/metabolism , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/metabolism , Male , Mice , Mice, Knockout , Middle Aged , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/physiology , Pedigree , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/metabolism , Polymorphism, Single Nucleotide/geneticsABSTRACT
OBJECTIVES: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry. METHODS: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months. TRIAL REGISTRATION: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). RESULTS: Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome. CONCLUSIONS: The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.
