Mechanistic immunological based classification of rheumatoid arthritis.

摘要: The classical autoimmunity paradigm in rheumatoid arthritis (RA) is strongly supported by immunogenetics suggesting follicular helper T-cell responses driving high titre specific autoantibodies that pre-dates disease onset. Using the immunological continuum model of inflammation against self with "pure" adaptive and innate immune at opposite boundaries, we propose a novel mechanistic classification describing heterogeneity within RA. Mutations or SNPs autoinflammatory genes including MEFV NOD2 are linked to seronegative RA phenotypes some so called palindromic cases. However, just as immunity closely functionally integrated, ACPA+ cases have superimposed "autoinflammatory" features abrupt onset attacks, severe self-limiting relevant mutations therapeutic pathway therapies colchicine IL-1 blockade. An emergent feature from this non-destructive phenotypes, both adaptive, epicentres situated extracapsular tissues. This mixed immunopathogenesis may be key understanding flares, resistant subsets unresponsive standard therapy for target component not currently considered expert recommendations.