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AB0992 Clinical and Immunological Markers of Poor Prognosis of Juvenile Arthritis
  1. L. Omelchenko,
  2. O. Oshlyans`ka,
  3. V. Chernyshov,
  4. I. Dudka
  1. IPOG NAMS Ukraine, Kyiv, Ukraine

Abstract

Background The pathomorphosis of juvenile arthritis observed in the last decade was linked to the modification of its definition to juvenile idiopathic arthritis (JIA). The transformation of the JIA-subtypes is possible. Knowing of poor prognosis markers at the onset of the disease can facilitate early use of targeted therapy.

Objectives To study the markers of the poor prognosis and their prognostic value using JIA-registry data.

Methods JIA registry data analysis including catamnesis data has been performed. Immune response was studied using lymphocytis subpopulations count measured by three-color flow cytoflyuorymetry, cytokines and antibodies levels studied by ELISA). Parameters that were suspicious to be poor prognosis markers were studied by discriminant and multivariate correlation analysis. Informational value (IV) analysis (Ixi) was performed using Kulbak formula calculation. Descriptive statistics presented as mean ± SD.

Results Records of 439 patients (230 males) were analyzed. Following factors were found to be poor prognosis predictors: age at onset of disease ≤5 years (Ixi =13,59), family history of rheumatic diseases (Ixi=1,04), laboratory high disease activity (especially ESR, CRP) (Ixi=47,12 for systemic JIA (sJIA), and 36,25 for other variants), high clinical activity (active joints count at the onset of the disease ≥5 (Ixi=20,61 for all subtypes), spine involvement at onset (Ixi=2,16 for sJIA and 4.89 for other), osteoporosis (Ixi=6,61 and 1,81 respectively) and functional impairments during the first 6 months (Ixi=3,91 and 3,09 respectively). The pooled IV of risk factors ≥20 correlated with severe course of JIA (Wald 99% probability). Intercurrent infections, lesions of reticuloendothelial system, internals involvement weren't recognized as poor prognosis predictors. The most relevant immunologic poor prognosis predictors were defined as: monocytosis (p=0,03); increase of CIC (p<0,001), immunoregulatory index (p=0,018), ANA titers (p<0,001), total Ig count (p=0,03), HLA DR+ (p=0,006) and CD25+ (p=0,001) T-cells presence, CD3+CD25+CD127low cells (p<0,001), CD3-CD56+CD8+ (p=0,001). Children with sJIA characterized by activated phagocytosis and humoral immunity (CD3-CD19+=927±24 cells/ml, total Ig 19,92±0,63 g/l, CIC increased to 0,089±0,043 g/l), serum IL1 increased to 22,5±3,1 pg/mI and IL6 to 24,4±4,7 pg/ml (correlated with the B-cells count (r=+0,62) and Ig (r=+0,78), CD3-CD19+CD5+ (r=-0,81) and monocytosis (r=+0,79). pJIA-subtype characterized by predominance of T-cell immune response: lymphocytosis, increase CD3+CD4+ to 67,7±5%, TNF-α to 16,3±3,7 pg/ml in proportion Th (r=+0,78), maximal RF detected (19,4%) and CCP antibodies (36,1%). Elevations of IL1 and TNF-α levels were found as poor prognostic factors only in sJIA (IL1 p=0,009) and pJIA subtypes (TNF-α p=0,05). Other JIA subtypes didn't show any specific abnormal immunological patterns. The discriminate function that summarizes the poor prognostic factors IV and their prognostic relevance was described.

Conclusions Identified high-relevant markers of poor prognosis and their informational (prognostic) value can be used for the development of targeted treatment tactics in patients with JIA.

Disclosure of Interest None declared

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