What is the role of cellular response in the pathophysiology of relapsing polychondritis (RP)?

Updated: Dec 24, 2020
  • Author: Nicholas Compton, MD; Chief Editor: Herbert S Diamond, MD  more...
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Although an inflammatory infiltrate of lymphocytes and neutrophils is the dominant histopathologic feature of relapsing polychondritis, little attention has been paid to the possible role of cellular immune responses in this condition. The association of relapsing polychondritis with HLA-DR4 also suggests an autoimmune pathogenesis. Individuals with HLA-DR4 were found to have a relative risk of 2 for developing relapsing polychondritis. The studies suggest the role of genetic factors in determining risk for developing relapsing polychondritis.

An elegant double-transgenic mouse model provides further evidence that HLA associations are important in the development of relapsing polychondritis. The model demonstrated that more than one HLA class II molecule might be required for expression of susceptibility. The model suggests an important role for cell-mediated immune responses and provides a means for acquiring a detailed understanding of its pathogenesis.

Natural killer T (NKT) cells, lymphocytes discrete from other T, B, and natural killer cells, come in two varieties: CD4+ and CD4-/CD8-. Antigen-presenting cells present antigen to the NKT cells via the major histocompatibility complex–like molecule CD1d. NKT cells are decreased in number and function in several other autoimmune diseases, including multiple sclerosis, RA, systemic lupus erythematosus, systemic sclerosis, and type 1 diabetes mellitus.

Researchers have quantified CD4-/CD8- and CD4+ V-alpha+ V-beta11+ NKT cells and found them decreased in patients with active or quiescent relapsing polychondritis compared with healthy controls. Analysis of the secreted cytokine profile and of binding of alpha-galactosylceramide–loaded CD1d to NKT cells suggests that CD4+ NKT cells play an important role in T1-helper responsiveness in patients with relapsing polychondritis. [10]

Serum levels of 17 cytokines from 22 patients with relapsing polychondritis experiencing a clinical flare were compared with those in age-matched controls. Three of the cytokines, interleukin 8, macrophage inflammatory protein 1-alpha, and monocyte chemoattractant protein-1, were found to be significantly elevated in patients with relapsing polychondritis. All 3 chemokines are proinflammatory and result in accumulation and activation of neutrophils, eosinophils, and monocytes/macrophages. [11]

Additionally, a group of researchers found T cells directed against collagen type II in one patient. A T-cell clone was identified and was found to be specific for a certain region of the collagen type II peptide. This research indicates that a T-cell response to collagen type II may play a role. [12]

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