Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Identification of NLRP1 as a Systemic Sclerosis Susceptibility Gene: A New Clue for the Contribution of Innate Immunity in SSc Pathogenesis.

Dieude7,  Philippe, Guedj4,  Mickaël, Wipff6,  Julien, Riemekasten2,  Gabriela, Airo8,  Paolo, Melchers1,  Inga, Matucci-Cerinic10,  Marco

Clinical Research Unit for Rheumatology, University Medical Center, Freiburg, Germany
University of Florence, Firenze, Italy
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Schumannstr. 20/21, D-10117, Berlin, Germany
Hopitaux de Paris Cochin, Paris, France
Laboratoire Statistique et Génome, UMR CNRS-8071/INRA-1152/Université d'Evry Val d'Essonne, France
National Scleroderma Centre, Lille Cedex, France
Paris Descartes University, Department of Rheumatology A, Cochin Hospital, Paris, France
Paris Diderot University, Department of Rheumatology, Bichat Claude Bernard Hospital, APHP, Paris, France
Rheumatology and Clinical Immunology, Spedali Civili, Brescia, Italy
Saint Quentin Yvelines University, Laboratoire de Biochimie Hormonale et Génétique, Ambroise Paré Hospital, AP-HP, Boulogne, France


Recent evidence has highlighted a potential role of interleukin 1 beta (IL-1b) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1b. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.


To test for association the NLRP1 SNPs rs6502867, rs26706600, rs8182352, rs12150220, rs4790797 with SSc in the European Caucasian population.


NLRP1 SNPs were genotyped in 3227 individuals comprising a Discovery set (870 SSc patients and 962 controls) and a Replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.


Conditional analyses revealed a significant association only for the NLRP1 rs8182352 variant. Both the NLRP1 rs8182352 C allele variant and the CC genotype were found to be associated with SSc-related fibrosing alveolitis (FA+) in the combined population: OR 1.19 95% CI [1.05–1.36], P=0.0065 and OR 1.43 95% CI [1.10–1.84], P=0.0063, respectively. Significant differences were also found when the FA+ SSc patients were compared to the FA- SSc patients. Linear regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related fibrosing alveolitis.


Our results establish NLRP1 as a new genetic susceptibility factor for SSc. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA+ SSc sub-phenotype, which represents a severe subset of the disease.

To cite this abstract, please use the following information:
Dieude, Philippe, Guedj, Mickaël, Wipff, Julien, Riemekasten, Gabriela, Airo, Paolo, Melchers, Inga, et al; Identification of NLRP1 as a Systemic Sclerosis Susceptibility Gene: A New Clue for the Contribution of Innate Immunity in SSc Pathogenesis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2226
DOI: 10.1002/art.29990

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