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Relationship of Specific IgM Responses with Infection and Lymphoproliferative Disease in Common Variable Immunodeficiency.
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Tukisa D. Smith, M.D., M.S., Paul J. Maglione, M.D., Ph.D., Charlotte Cunningham-Rundles, M.D., Ph.D.
Rationale: While common variable immunodeficiency (CVID) markedly impairs IgA and IgG responses, IgM production is retained in some patients. This retained IgM production is linked with protection against infection as well as susceptibility to lymphoproliferative complications. To gain more insight into the role of IgM in CVID, we examined whether antigen-specific IgM levels differentiated patients with history of pneumonia or those with lymphoproliferative complications.

Methods: Serum IgM recognizing bacterial (capsular polysaccharides, cell wall polysaccharides, flagellin, lipopolysaccharide) or natural IgM (forssman antigen, phosphocholine) antigens were measured by enzyme-linked immunosorbent assay. Patients meeting consensus guidelines for CVID as well as age-matched controls were included in this study. Retrospective chart review was utilized to determine history of infections and other medical complications. This study was approved by the institutional review board of the Icahn School of Medicine at Mount Sinai.

Results: Compared to CVID patients without history of pneumonia, those with history of pneumonia had significantly lower levels of IgM recognizing bacterial cell wall antigens and flagellin, but interestingly had similar levels of IgM recognizing pneumococcal capsular polysaccharides. In contrast, significant reduction of serum IgM recognizing pneumococcal capsular polysaccharides was found in CVID patients with lymphoproliferative complications compared than those without.

Conclusions: Levels of serum IgM recognizing specific antigens can differentiate CVID patients with history of pneumonia or lymphoproliferative complications. This may reconcile the fact that higher IgM levels have been linked to both protection against infection and susceptibility to lymphoproliferative disease as the specificity of these IgM responses appears to be significant.