Cytokine/adipokine profile shows no evidence of an inflammatory or metabolic basis for incident erosive hand oa in the osteoarthritis initiative cohort

Purpose: Erosive Hand OA (eHOA) is a painful, age-related destructive arthritis of interphalangeal joints that severely impairs manipulative activities of daily life. Observations that erosive Hand OA is often associated with generalized OA, and with clinical inflammation, have predicated conjecture of a systemic inflammo-metabolic pathogenesis. We tested for associations of inflammation and metabolic biomarkers in the OAI cohort. Methods: Using a nested case-cohort design among 3604 participants in the Osteoarthritis Initiative cohort who had dominant hand radiographs obtained at baseline and month 48, we selected all individuals who developed incident erosive Hand OA during the 4-year observation period; and an OAI-representative random sample of 1350 participants. Interphalangeal (IP) and metacarpophalangeal (MCP) joints were scored for KL grade and presence of central erosions (OARSI atlas). Biospecimens were collected at baseline. Erosive Hand OA was defined in persons with at ≥1 IP or MCP joints with KL ≥2 and a central erosion. Symptomatic eHOA was defined by presence of erosive Hand OA with reported hand pain, aching or stiffness on most days during the past 30 days. Incidence for each outcome was defined when an individual had erosive Hand OA or symptomatic eHOA at 48-months but not baseline.Serum biomarkers of inflammation (hs-CRP, cytokines interleukin [IL]-1β, IL-5, IL-7, IL-8, IL-18), insulin resistance and dysglycemia (glucose, insulin, glycated serum protein [GSP]), and adipokines (resistin, adiponectin, leptin) were measured using immunoassays (ELISA, chemiluminimescence, and patterned array technology) and enzymatic colorimetric procedures, blinded to case status. We analyzed log transformed baseline biomarker levels as a predictor for erosive Hand OA incidence at 48 months taking into account the case-cohort design using a weighted discrete Cox regression model to control for confounders. Results: 86 participants developed incident erosive Hand OA and 133 developed incident symptomatic eHOA. Individuals who developed erosive Hand OA had substantially different characteristics from controls, especially in age (64.1 vs. 60.3 yrs p=0.02), gender (73 vs. 56% female p=0.02), race (4 vs. 16% Black p=0.10) hand OA severity (5.9 vs. 1.8 joints p<0.001), hand pain prevalence (46 vs. 18% p<0.001), and lower physical activity (PASE score 145 vs. 168 p= 0.002). In the multivariate analyses, only hsCRP, IL-7 and IL-8 levels were consistently associated with incident erosive Hand OA (Table). Associations with incident symptomatic eHOA were consistent for IL-7 (HR per SD =1.32 [95%CI 1.11, 1.56], p trend 0.003) and also showed an association with IL-8 (HR per SD =1.29 [95%CI 1.08, 1.54], p trend 0.011) but not with hsCRP. There was no association with dysglycemia; or with adipokines. Conclusions: Erosive Hand OA incidence is strongly associated with age, female gender, and OA severity, but does not seem to occur in a milieu of systemic inflammation or metabolic derangement. We did find a specific association with interleukin-7, a cytokine that appears to promote joint tissue destruction via direct effects on IL-7R-expressing chondrocytes. These observations suggest that erosive Hand OA is instead a product of the local articular environment and that IL-7, and possibly IL-8, may have a role in its pathogenesis.Tabled 1CYTOKINE & ADIPOKINE LEVELS AND EHOA INCIDENCE; ADJUSTED FOR AGE, GENDER, BMI, RACEeHOANo eHOAHR per SDHR for TERTILES (95% CI)mean (se)mean (se)(95% CI)MIDHIGHp trendhs-CRP (mg/L)1.74 (1.03)1.99 (1.25)1.22 (0.95, 1.55)1.43 (0.79, 2.61)2.04 (1.12, 3.69)0.02IL-18 (pg/mL)588 (1.01)679 (1.10)1.19 (0.99, 1.44)1.16 (0.64, 2.11)1.66 (0.94, 2.94)0.09IL-7 (pg/mL)12.98 (1.01)15.03 (1.08)1.43 (1.19, 1.71)1.49 (0.80, 2.76)2.59 (1.44, 4.67)<0.01IL-8 (pg/mL)13.67 (1.01)15.02 (1.08)1.17 (0.97, 1.42)1.53 (0.81, 2.90)1.85 (1.00, 3.43)0.05IL-1b (pg/mL)0.28 (1.01)0.32 (1.08)0.99 (0.81, 1.21)1.03 (0.58, 1.83)1.04 (0.60, 1.82)0.88IL-5 (pg/mL)0.78 (1.02)0.78 (1.13)0.97 (0.74, 1.27)0.83 (0.47, 1.45)0.81 (0.46, 1.41)0.44Glucose (mg/dL)100.0 (1.00)96.4 (1.03)0.95 (0.71, 1.26)0.58 (0.32, 1.05)0.94 (0.53, 1.66)0.82Insulin (uIU/mL)9.03 (1.02)8.79 (1.13)1.06 (0.82, 1.36)1.09 (0.61, 1.97)1.05 (0.54, 2.02)0.86GSP (umol/L)246 (1.01)242 (1.04)1.00 (0.79, 1.28)0.77 (0.44, 1.35)0.84 (0.48, 1.50)0.61Resistin (ng/mL)8.88 (1.01)9.39 (1.08)1.05 (0.83, 1.34)1.05 (0.56, 1.96)1.68 (0.97, 2.89)0.06Adiponectin (ng/mL)7330 (1.02)7270 (1.12)0.89 (0.66, 1.21)1.11 (0.60, 2.06)0.68 (0.34, 1.37)0.19Leptin (pg/mL)14677 (1.02)17321 (1.13)1.45 (0.99, 2.14)1.12 (0.57, 2.20)1.25 (0.54, 2.90)0.61 Open table in a new tab