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

Abstract

Background: Complement 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 and methods: CD55 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.

Results: Interestingly, 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).

Conclusions: This 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.

Figure 1

(A) Patient (RA) with isolated CD55 (DAF) red-cell deficiency (10% of his total red-cell population), CD55(−)/CD59(+). (B) Patient (SeA) with concomitant CD55 (DAF) and CD59 (MIRL) red-cell deficiency (10%/25%, of his total red-cell population, respectively), CD55(−)/CD59(−). None of these patients had positive Ham or sucrose test.

Figure 2

(A) Patient (Vsc) with concomitant CD55 (DAF) and CD59 (MIRL) red-cell deficiency (25%/10%, of his total red-cell population, respectively). 12/12 patients with Vsc presented with “PNH-like” red-cell phenotype. However, only 7 (6.2%) patients on this study were presented with this red-cell phenotype of CD55/CD59 percentage-deficiency. (B) Patient (Sc) with concomitant CD55 (DAF) and CD59 (MIRL) red-cell deficiency (10%/10%, of his total red-cell population, respectively). 30.1% of patients were presented with this red-cell phenotype of CD55/CD59 percentage-deficiency. None of these patients had positive Ham or sucrose test, for PNH.

Figure 3

Scatter diagram with regression line between CD55% red-cell deficiency and Hb levels (g/dl), in rheumatologic patients. Regression equation: y=13.2812 + −0.1974 × + 0.005348 x², Coefficient of determination R²=0.05237, F=3.0398, p=0.052.

Figure 4

Scatter diagram with regression line between CD59% red-cell deficiency and Hb levels (g/dl), in rheumatologic patients. Regression equation: y=11.8458 + 0.02284 × + 0.0007997 x², Coefficient of determination R²=0.01338, F=0.7456, p=0.477.

Figure 5

Scatter diagram with regression line between neutrophils’ total population (×10⁶/lt) and Hb levels (g/dl) in patients with concomitant CD55/CD59 deficiency. Regression equation: Log(y)=4.0642 + −0.03645 x, Coefficient of determination R²=0.1167, F=5.8137, p=0.020.

Figure 6

Scatter diagram with regression line between Hb levels (g/dl) and lymphocytes’ total population (×10⁶/lt) in patients with concomitant CD55/CD59 deficiency. Regression equation: y=10.9051 + 0.0008468 x, Coefficient of determination R²=0.09902, F=4.836, p=0.033.

Figure 7

PNH patient: >75% simultaneous absence of CD55 (DAF) and CD59 (MIRL). This patient had a positive Ham and sucrose test.