Research article
Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies
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* Corresponding authors: Minoru Satoh Minoru.Satoh@medicine.ufl.edu - Mónica Vázquez del Mercado dravme@hotmail.com
1 Departamento de Biología Molecular y Genómica, Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético (IIRSME), Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara, Jalisco, CP 44340, México
2 Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, P.O. Box 100221, Gainesville, FL 32610-0221, USA
3 Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, P.O. Box 100221, Gainesville, FL 32610-0221, USA
4 Department of Oral Biology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0424, USA
5 Departamento de Inmunología y Reumatología del Hospital General de Occidente, Secretaría de Salud Jalisco, Av. Zoquipan 1050, CP 45100, Zapopan, Jalisco, México
6 División de Investigación, Hospital de Especialidades, CMNO, IMSS, and Deparamento de Fisiología, CUCS, Universidad de Guadalajara, Sierra Mojada 950, CP 4430, Guadalajara, Jalisco, México
7 Departamento de Reumatología, Instituto Nacional en Ciencias Médicas y de la Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan C.P. 14000, Mexico, DF, México
8 División de Medicina Interna, Departamento de Reumatología, Hospital Civil Juan I Menchaca, Salvador de Quevedo y Zubieta N° 750, CP 44340, Guadalajara, Jalisco, México
Arthritis Research & Therapy 2009, 11:R27 doi:10.1186/ar2621
Published: 20 February 2009Abstract
Introduction
Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA–protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein–Barr virus in the pathogenesis has been suggested. Similar to Epstein–Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1–70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus.
Methods
Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein–Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1–70 k, P peptide, rheumatoid factor, dsDNA, β2-glycoprotein I).
Results
IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV(+) group (n = 20) versus the IgM anti-CMV(-)IgG (+) (n = 39) group were compared. Most (19/20) of the IgM anti-CMV(+) cases were IgG anti-CMV(+), consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein–Barr virus–viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV(+) group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1–70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA–protein complex (P = 0.0077).
Conclusions
Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis.