The presence of CD55- and/or CD59-deficient erythrocytic populations in patients with rheumatic diseases reflects an immune-mediated bone-marrow derived phenomenon

Abstract

BackgroundComplement has the potential to provoke severe impairment to host tissues, as shown in autoimmune diseases where complement activation has been associated with diminished CD55 and/or CD59 expression on peripheral blood cell membranes. The aim of this study was to evaluate the presence of CD55- and/or CD59-deficient erythrocytic populations in patients with different rheumatic diseases and to investigate possible correlations with clinical or laboratory parameters.Material/MethodsCD55 and CD59 expression was evaluated in erythrocytes of 113 patients with rheumatic diseases, 121 normal individuals, and 10 patients with paroxysmal nocturnal hemoglobinuria (PNH) using the Sephacryl gel microtyping system. Ham and sucrose tests were also performed.ResultsInterestingly, the majority of patients (104/113, 92%) demonstrated CD55- and/or CD59-deficient erythrocytes: 47 (41.6%) with concomitant deficiency of CD55 and CD59, 50 (44.2%) with isolated deficiency of CD55, and 6 (6.2%) with isolated deficiency of CD59. In normal individuals, only 2 (1%) had concomitant CD55/CD59 negativity and 3 (2%) had isolated CD55 or CD59 deficiency. All PNH patients exhibited simultaneous CD55/CD59 deficiency. Positive Ham and sucrose tests were found only in PNH patients. There was no association between the CD55- and/or CD59-deficient erythrocytes and hemocytopenias or undergoing treatment. However, CD55 expression significantly influenced hemoglobin values (F=6.092, p=0.015).ConclusionsThis study provides evidence supporting the presence of erythrocytes with CD55 and/or CD59 deficiency in patients with rheumatic diseases. Moreover, CD55 deficiency on red cells influences hemoglobin concentration. Further studies using molecular techniques will clarify the exact pathophysiological mechanisms of this deficiency.

Altered Expression of Complement Regulatory Proteins CD35, CD46, CD55, and CD59 on Leukocyte Subsets in Individuals Suffering From Coronary Artery Disease

“…It is plausible that this could have aggravated the complement activation and related pathological manifestations in patients with CAD. A disease related decline in Cregs has earlier been reported in Rheumatoid arthritis (RA) (24, 25). Herein, we observed a significantly high surface expression of CD35 on granulocytes and of CD59 on lymphocytes and granulocytes of CAD patients.…”

“…Membrane complement regulatory proteins are expressed widely on different cell populations. Dysregulation of the Cregs, proteins responsible for maintaining homeostasis of the complement cascade, has been implicated in several autoimmune disorders, chronic inflammatory diseases, diabetes, cancers and malaria (11, 16, 18, 24, 25). Unabated activation of the complement cascade and increased expression of inflammatory cytokines contribute significantly to the immune inflammatory manifestations in CAD (4, 26, 27).…”

Complement in Sickle Cell Disease: Are We Ready for Prime Time?

“…These proteins propagate complement-mediated cell lysis and their deficiency or dysfunction has been associated with the pathophysiology of other diseases as well. [49][50][51][52][53] Most studies have focused on surface-bound complement regulators -CD55, CD59, CD46 and CR1 -. In the frame of SCD, some studies revealed decreased CD55 and CD59 on sickled erythrocytes, in comparison with control subjects.…”