Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations

• Published in: European journal of human genetics : EJHG Vol. 9; no. 11; pp. 849 - 854
• Main Authors: Medlej-Hashim, M, Petit, I, Adib, S, Chouery, E, Salem, N, Delague, V, Rawashdeh, M, Mansour, I, Lefranc, G, Naman, R, Loiselet, J, Lecron, J C, Serre, J L, Mégarbané, A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2001
• Subjects: Arthritis; Blood & organ donations; Colchicine; Consortia; Cytoskeletal Proteins; DNA - genetics; Familial Mediterranean fever; Familial Mediterranean Fever - blood; Familial Mediterranean Fever - genetics; Familial Mediterranean Fever - pathology; Fever; Genetics; Genotype; Genotypes; Heterozygotes; Homozygotes; Humans; Immunoglobulin D; Immunoglobulin D - blood; Immunoglobulins; Kinases; Mutation; Mutation, Missense; Pain; Phenotypes; Plasma levels; Proteins - genetics; Pyrin; Pyrin protein; Serum levels; Severity of Illness Index; Lebanon; Beirut Lebanon; Kuwait; France
• DOI: 10.1038/sj.ejhg.5200725
• ISSN: 1018-4813

Familial Mediterranean Fever (FMF) is a recessively inherited disorder, characterized by episodic fever, abdominal and arthritic pain, as well as other forms of inflammation. Some FMF patients present higher IgD serum levels, and it is not yet known whether such an elevation is related to specific genotypes or correlated with a specific phenotype. In order to evaluate the association between known FMF-related mutations and IgD levels in confirmed patients, as well as the correlation between those levels and the presence of specific clinical signs, genotypic analysis and IgD plasma measurements were performed for 148 Lebanese and Jordanian FMF patients. Most common mutational patterns were M694V heterozygotes (19%) and homozygotes (17%), and V726A heterozygotes (18%) and homozygotes (5%), with an additional 11% combining both mutations. Twenty-one patients had higher IgD levels (superior to 100 microg/ml). The risk for higher IgD levels was significantly associated with M694V homozygote status (OR = 6.25) but not with heterozygotic one (OR = 1). Similarly, the risk for higher IgD was also found with V726A homozygotes (OR = 2.2) but not with heterozygotes (OR = 1.05). The use of colchicine was not statistically associated with IgD levels. Clinically, hyper IgD was also found significantly associated with arthritis (OR = 18). Thus, homozygotic status for M694V, and to a lesser extent V726A, is associated with increased risk for higher IgD plasma levels, regardless of colchicine use. Elevated IgD plasma levels are also correlated with the severity of FMF manifestations, and especially with arthritis.