Soluble CD 30 in primary Sjögren ’ s syndrome

Sir, We read with interest the paper by Ichikawa et al. reporting high serum levels of the soluble form of the CD30 molecule (sCD30) in primary Sjögren’s syndrome (SS) (1). This finding is in line with the increased levels we described in other autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc) (2-4). Although the CD30 surface molecule is expressed not only by T lymphocytes and its significance as marker of a distinct T cell subpopulation secreting Th2-type cytokines is still controversial (5-8), it is not unreasonable to postulate that the high serum levels of sCD30 detected in autoimmune diseases may reflect an activation of CD30+ T cells at the sites of inflammation. This assumption is supported by the demonstration of T cells expressing the CD30 surface molecule in the synovial fluid of RA, in the ascitic effusion of SLE and in the skin of SSc patients (2, 3, 9). In SS, however, this conclusion is less straightforward. In a large series of patients examined at the University of Perugia (60 females, 7 males), who fulfilled the Vitali’s criteria for primary SS (10), we confirmed that sCD30 serum levels (Ki-1 antigen ELISA,Dako A/S, Glostrup, Denmark) are higher in SS (median, range: 46.5 U/ml, 10-252) than in sexand agematched controls (n. 58, 12 U/ml, 5-31 p < 0.001). However, we failed to find CD30+ cells in 22 peripheral blood samples (flow cytometry, FACS, Becton Dickinson, San José, CA) as well as in 6 minor salivary gland tissue specimens, analyzed by a described immunohistologic technique (11), in our SS patients. This negative finding may be due to the fact that activated CD30+ cells are operating in other sites, such as lymphoid organs. Alternatively, CD30+ cells may either lack adhesion molecules able to firmly anchor them to the inflamed tissue or rapidly lose the molecule from their surface by shedding. In contrast to Ichikawa’s data, in our study the sCD30 values correlated well with rheumatoid factor (RF, p < 0.01; r = 0.42), but not with IgG, IgA and IgM values (laser nephelometry). We confirmed, on the other hand, that SS patients positive for fluorescent antinuclear antibodies (ANA) display higher sCD30 levels compared to the group of ANAnegative SS patients (p < 0.001). In particular, patients with circulating anti-Ro (SSA) and anti-La (SSB) antibodies (counterimmunoelectrophoresis) showed the highest sCD30 values (Fig. 1). In our opinion, these findings are relevant for two reasons. First, RF, ANA and antiRo/La antibodies are able to distinguish those cases of SS in which T cells are actively involved (12). Second, antiLa antibodies represent the best marker of exocrine gland inflammation and are strictly associated with the degree of glandular lymphoid infiltration (13). Thus, higher serum levels of sCD30 in SS may actually reflect an involvement of CD30+ T cells in the course of the chronic inflammatory autoimmune process characterizing the disease. The functional role exerted by this T cell subset in modulating the activity of systemic autoimmune disorders remains, however, unclarified. In contrast to our observations, Ichikawa et al. did not find any correlation between sCD30 levels and parameters of disease activity in RA and SLE. This is difficult to interpret in RA on the basis of the documented presence of CD30+ T cells in the joint effusion (3). The discrepancy with our SLE patients may be explained, at least in part, by different disease severity and organ involvement. In this setting, it is interesting to note that SLE patients with renal involvement usually have low levels of sCD30, as already reported (2) and confirmed by additional studies in a larger group of SLE patients followed for several months, while joint and skin involvement seems to be associated with high sCD30 values (unpublished observations). In conclusion, we believe that our and Ichikawa’s findings support an involvement of CD30+ T cells in systemic autoimmune diseases, even if they do not clarify their functional role in these disorders. Although the concept that Th1/Th2 cell balance plays a key role in determining activation or remission of autoimmune diseases is a fascinating possibility supported by several experimental findings (reviewed in refs. 14, 15), the relevance of sCD30 as marker of Th0/Th2 cell activation and/or disease activity in these diseases is still unproven and needs additional studies. A better understanding of the role of the CD30 molecule on the surface of T cells may provide new insight into the role exerted by CD30+ T cells in systemic autoimmune disorders.