Premium
Cryoglobulin‐induced cytokine production via Fc γ RIIa: inverse effects of complement blockade on the production of TNF‐ α and IL‐10. Implications for the growth of malignant B‐cell clones
Author(s) -
Mathsson Linda,
Tejde Andreas,
Carlson Kristina,
Höglund Martin,
Nilsson Bo,
NilssonEkdahl Kristina,
Rönnelid Johan
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05538.x
Subject(s) - cytokine , immunology , lymphoproliferative disorders , biology , antibody , lymphoma
Summary Monoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance with our findings of IC‐induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures. In separate experiments temperature and ionic strength were varied, or Fc γ RIIa, Fc γ RIII and complement activation were blocked; supernatant cytokine levels were then determined by enzyme‐linked immunosorbent assay. CG‐induced cytokine production from monocytes varied with precipitation induced by changes in temperature and ionic strength and was mediated via Fc γ RIIa‐ and complement‐dependent mechanisms. Complement blockade resulted in increased IgG CG‐induced interleukin (IL)‐10 production that was inversely correlated with decreased production of tumour necrosis factor‐ α . CG‐induced IL‐10 might be a growth factor for malignant B‐lymphocytes in CG‐associated lymphoproliferative diseases with constant complement consumption. Knowledge of mechanisms underlying CG‐induced cytokine production can be useful for designing treatments for type I CG‐associated pathology in lymphoproliferative diseases.