A high migratory capacity of donor T-cells in response to the lymph node homing receptor CCR7 increases the incidence and severity of GvHD.

The pathogenesis of GvHD involves migration of donor T-cells into the secondary lymphoid organs in the recipient, which is steered by two homing molecules, CD62L and CCR7. Therefore, we investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor-recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD. Similarly, the acute GvHD (aGvHD) group received higher percentage of CD4+CCR7+ T-cells, whereas chronic GvHD (cGvHD) patients were transplanted with higher percentages of CD8+CCR7+ T-cells compared with the non-GvHD group. These results were confirmed when patients were subdivided according to degrees of severity. Further, multivariate analysis confirmed that the proportions of CCR7+ CD4+ and CCR7+ CD8+ T-cells are risk factors for the development and severity of aGvHD and cGvHD, respectively. Functional experiments demonstrated that CCR7+ T-cells exhibited higher potential for activation than CCR7- T-cells did. We therefore propose that the selective depletion of CCR7-expressing T-cells may be an effective preventive therapy for GvHD.

Autoantibodies against TIF-1-γ and CADM-140 in Spanish patients with clinically amyopathic dermatomyositis (CADM): clinical significance and diagnostic utility.

BACKGROUND: Patients with clinically amyopathic dermatomyositis (CADM) appear to be at risk for developing cancer and interstitial lung diseases, but population data to confirm this hypothesis are limited. Moreover, CADM presents cutaneous and histological findings that may overlap with subacute cutaneous lupus erythematosus (SCLE). OBJECTIVES: To determine the association between myositis-specific autoantibodies, myositis-associated autoantibodies and CADM in Spanish patients. In addition, to study the usefulness of these autoantibodies in the differential diagnosis between CADM and SCLE. METHODS: Serum samples were tested for myositis-specific autoantibodies and myositis-associated autoantibodies through immunoprecipitation and other standardized methods. RESULTS: Anti-CADM-p140 and anti-p155 antibodies were the only myositis-specific autoantibodies found and were associated with interstitial lung diseases and cancer respectively. No myositis-associated autoantibodies were found in CADM. Moreover, clinical subsets and proportions seemed to differ from Asian cohorts, where anti-CADM-p140 is considered a CADM hallmark antibody and a risk factor for the development of interstitial lung disease. Interestingly, anti-SSA was highly associated with SCLE, whereas no myositis-specific autoantibodies were found in this entity. LIMITATIONS OF THE STUDY: Association between CADM and myositis-specific autoantibodies and differences between CADM and SCLE were tested on a relatively small cohort of patients. CONCLUSION: There is an association between cancer-associated myositis and interstitial lung diseases and their hallmark autoantibodies in our cohort. In addition, the combined determination of myositis-specific autoantibodies and SSA autoantibodies may help to accurately discriminate SCLE from CADM.