CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis.
OBJECTIVE
CARD8 and NLRP3 are constituents of the inflammasome which regulates interleukin 1beta production. The influence of polymorphisms in CARD8 and NLRP3 on rheumatoid arthritis (RA) susceptibility and severity were evaluated.


METHODS
CARD8 p.C10X and NLRP3 p.Q705K genotypes were assessed in >500 controls and patients with early RA from northern Sweden. The patients were monitored regularly over a 2-year period. The 28-joint disease activity score (DAS28) and its separate components were compared across genotypes.


RESULTS
Patients with one or more variant alleles in CARD8 (CARD8-X) had increased DAS28, tender joint count and erythrocyte sedimentation rate during the 2-year follow-up period despite receiving disease-modifying antirheumatic drugs to a greater extent. CARD8-X was significantly over-represented among patients who received anti-tumour necrosis factor therapy during the first 2 years. CARD8 and NLRP3 genotypes did not influence radiological joint damage and were not associated with an increased susceptibility.


CONCLUSIONS
Carriage of CARD8-X is associated with a worse disease course in early RA.
Kastbom
Alf
A
Division of Rheumatology, Linköping University Hospital, Linköping, Sweden. alf.kastbom@liu.se
Johansson
Martin
M
Verma
Deepti
D
Söderkvist
Peter
P
Rantapää-Dahlqvist
Solbritt
S
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D001799:Blood Sedimentation; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D018450:Disease Progression; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic
D018501:Antirheumatic Agents; D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009363:Neoplasm Proteins