Decreased numbers of circulating plasmablasts and differences in IgA1-plasmablast homing to skin in coeliac disease and dermatitis herpetiformis.

The two clinical phenotypes of gluten enteropathy, coeliac disease (CD) and dermatitis herpetiformis (DH), were characterized for numbers and homing profiles of circulating final effector B cells, plasmablasts, identified as immunoglobulin (Ig)-secreting cells (ISC). In CD, the numbers of ISC were approximately 50% lower than in DH or controls. ISC expressed peripheral lymph node homing receptor (HR), L-selectin, less frequently in CD (54%) and DH (52%) patients than in controls (70%). The expression of gut mucosal HR, alpha(4)beta(7), was less frequent in CD (42%) than in DH (65%) or controls (60%). In DH, but not in CD or controls, a higher proportion of IgA1-ISC (40%) than IgA2-ISC (25%) expressed the skin HR, cutaneous lymphocyte-associated antigen. In gluten enteropathy circulating plasmablasts are more mature, but decreased in number, and have distorted homing profiles. Differential IgA1-plasmablast homing could be associated with the development of skin rash with IgA1-deposits in DH but not in CD.

Prediction of severe rheumatoid arthritis using Epstein-Barr virus.

One of the immunological abnormalities in patients with RA is increased synthesis of immunoglobulins (Ig) in cultures of Epstein-Barr virus (EBV-) stimulated lymphocytes. We set out to investigate whether this feature, seen early in the disease, associated with later severe RA. We studied prospectively 45 patients with recent onset RA and, 41 healthy individuals. From 0-6 months after admission, blood lymphocytes were cultured in the presence of EBV for 4 weeks and Ig in the supernatants were assayed. To assess the severity of disease, clinical, laboratory and radiological evaluations were performed every 6 months for 2 yr. The association of increased Ig production with the severity of RA was then analysed. During the follow-up period, 30 of the original 45 patients developed erosive disease. At onset, these 30 patients did not differ from the 15 with non-erosive disease when assessed by several parameters reflecting rheumatoid activity. However, EBV-induced production of Ig was significantly higher in the erosive compared with the non-erosive group of patients (P < 0.001). Using Ig synthesis, it was possible to identify a subgroup of 9-14 patients, depending on the isotype studied, who would later develop severe erosive disease (PVpos = 90-100%). These results show that high EBV-induced production of Ig early in RA associates with later severe disease, particularly with joint erosions. This feature identifies, with over 90% likelihood, the third of patients who will later develop most severe disease.

Association of in vitro immune functions with the severity of the disease in rheumatoid arthritis.

The production of immunoglobulins in vitro by lymphocytes from rheumatoid patients has been earlier shown to be defective. This report describes a 2-year follow up study which shows that this defect is associated with the severity of RA. Pokeweed mitogen and Staphylococcus aureus Cowan I were used to stimulate in vitro immunoglobulin production by lymphocytes from patients with recent onset RA, and the relationship of responses to clinical characteristics were studied. Impaired polyclonal IgM synthesis, already detectable at the onset of disease, associated with joint destructions observed after a 2-year follow up period. Further, phytohaemagglutinin-induced interleukin-2 (IL-2) release by the cells of patients with erosive disease was found to be reduced compared to cells from patients without eroded joints. The results indicate that altered immune functions--manifested as decreased production of IgM and IL-2--in RA are involved in the progression of the disease and affect the outcome of patients and, thus, represent an unfavourable prognostic feature.