Expression of some co-stimulatory molecules in systemic lupus erythematosus patients : association with clinical features

Abstract EN

Objective : to measure expression of the co-stimulatory molecules CD40L, CD40, CD28, CD80 and CD86 on peripheral blood lymphocytes in SLE patients and to correlate it with disease activity, levels of anti-ds-DNA antibodies and to detect their association with some clinical features of SLE.

Methodology : the study included 23 females with SLE diagnosed according to the 1982 revised criteria of the American College of Rheumatology for the diagnosis of SLE and 7 apparently healthy females with matched age to patients as a control group.

Patients were attending the outpatient clinics of Rheumatology and Rehabilitation and Internal Medicine departments in Ain Shams University Hospitals.

Patients were subjected to history taking, thorough clinical examination, disease activity was assessed using Systemic Lupus Erythematous Disease Activity Index (SLEDAI).

The SLE cumulative organ damage was scored using the Systemic Lupus International Collaborating Clinics (SLICC) damage index.

14 patients were considered to have active disease with SLEDAI score > 4 and 9 patients had a score of 4 or less was in remission.

The different clinical features of SLE patients were : 7 patients with renal disease, 6 patients with atherosclerosis presentation (myocardial infarction, angina pain, and stroke), 6 patients with articular manifestations and 4 patients with skin manifestations.

Patients and controls were subjected to laboratory investigations including: measurement of, hemoglobin level, anti-ds-DNA antibody titer, ESR, serum level of cretonne, lipid profile (cholesterol level, HDL cholesterol level, LDL cholesterol level, triglyceride level), level of proteinuria, expression of the activation markers CD25 for T cells and CD38 for B cells and the co-stimulatory molecules CD28, CD40 ligand (CD40L) on CD4 T cells and CD80, CD86, CD40 on CD19 B cells.

Results : lymphocytes of SLE patients showed signs of increased activation as indicated by the highly significant increase in CD25 and CD38 expression on CD4 T cells and CD19 B cells respectively in patients compared to controls (t = 2.9, t = 4.7 respectively) and in patients with active disease compared to those in remission (t = 5.3, t = 3.1 respectively).

The expression of the co-stimulatory molecules CD40L and CD86 on T and B cells respectively was significantly increased in patients when compared to controls (t = 2.1, t = 3.9 respectively) and in active versus inactive SLE patients (t = 8.1, t = 5.3 respectively).

The highest increase in CD40L and CD86 expression could be detected in SLE patients with renal disease and atherosclerosis compared to those with articular or skin manifestations.

In patients with SLE a highly significant positive correlation could be found between increased CD40L expression and SLEDAI (r = 0.79), anti-ds-DNA antibody titer (r = 0.90), CD25 expression (r = 0.70), CD86 expression (r=0.82).

Among SLE patients, enhanced CD86 expression showed highly significant positive correlation with SLEDAI (r = 0.58), anti-ds-DNA antibody titer (r = 0.76), CD38 expression (r = 0.75).

A significant positive correlation could be found between increased CD40L expression and serum cretonne level (r = 0.81) on one hand, and serum cholesterol level (r = 0.94) on the other hand among SLE patients with renal disease and atherosclerosis respectively.

Conclusion: The CD40L / CD40 and CD28 / CD86-CD80 pathways of co-stimulatory molecules are interrelated in lymphocytes of patients with SLE ; they may play an important role in immunopathogenesis of SLE.

Increased expression of CD40L and CD86 on T and B cells respectively showed significant positive correlations with disease activity, anti-ds-DNA antibody titer and they also showed association with some clinical features of SLE especially nephritis and atherosclerosis clinical manifestations.

Anti-co-stimulatory molecules monoclonal antibodies may be important therapeutic targets in SLE.