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

Abstract

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.

Fig. 1

Circulating effector B cells in gluten enteropathies. The number of immunoglobulin-secreting cells in immunoglobulin (Ig)A-, IgM- and IgG-isotypes among peripheral blood mononuclear cells in patients with coeliac disease, dermatitis herpetiformis and in healthy controls. Error bars indicate standard error of mean. Asterisks indicate statistical significance by Student's t-test (*P < 0·05; **P < 0·01; ***P < 0·001).

Fig. 2

The expression of various homing receptors and adhesion molecules on circulating immunoglobulin-secreting cells of different isotypes in coeliac disease, dermatitis herpetiformis and in healthy controls. Error bars indicate standard deviation. The numbers of volunteers from whom the data were pooled are given under each bar. (a) α₄β₇-integrin, (b) L-selectin, (c) α₄-chain. Asterisks indicate statistical significance by Student's t-test (*P < 0·05; **P < 0·01; ***P < 0·001).

Fig. 3

The expression of homing receptors on immunoglobulin (Ig)A1- and IgA2-secreting cells in coeliac disease, dermatitis herpetiformis and in healthy controls. Error bars indicate standard deviation. The numbers of volunteers from whom the data were pooled are given under each bar. (a) α₄β₇-integrin, (b) cutaneous lymphocyte-associated antigen, (c) L-selectin, (d) α_eβ₇-integrin. Asterisks indicate statistical significance by paired Student's t-test (*P < 0·05; **P < 0·01; ***P < 0·001).