Marta Crespo

Acute humoral rejection in renal allograft recipients: I. Incidence, serology and clinical characteristics.

Background. Acute rejection (AR) associated with de novo production of donor-specific antibodies (DSA) is a clinicopathological entity that carries a poor prognosis (acute humoral rejection, AHR). The aim of this study was to determine the incidence and clinical characteristics of AHR in renal allograft recipients, and to further analyze the antibodies involved. Methods. During a 4-year period, 232 renal transplants (Tx) were performed at our institution. Assays for DSA included T and B cell cytotoxic and/or flow cytometric cross-matches and cytotoxic antibody screens (PRA). C4d complement staining was performed on frozen biopsy tissue. Results. A total of 81 patients (35%) suffered at least one episode of AR within the first 3 months: 51 had steroid-insensitive AR whereas the remaining 30 had steroid-sensitive AR. No DSA were found in patients with steroid-sensitive AR. In contrast, circulating DSA were found in 19/51 patients (37%) with steroid-insensitive AR, and widespread C4d deposits in peritubular capillaries were present in 18 of these 19 (95%). In at least three cases, antibodies were against donor HLA class II antigens. DSA were not found in the remaining 32 patients but C4d staining was positive in 2 of 32. The DSA/C4d positive (n=18) and DSA/C4d negative (n=30) groups differed in pre-Tx PRA levels, percentage of re-Tx patients, refractoriness to antilymphocyte therapy, and outcome. Plasmapheresis and tacrolimus-mycophenolate mofetil rescue reversed rejection in 9 of 10 recipients with refractory AHR. Conclusion. More than one-third of the patients with steroid-insensitive AR had evidence of AHR, often resistant to antilymphocyte therapy. Most cases (95%) with DSA at the time of rejection had widespread C4d deposits in peritubular capillaries, suggesting a pathogenic role of the circulating alloantibody. Combined DSA testing and C4d staining provides a useful approach for the early diagnosis of AHR, a condition that often necessitates a more intensive therapeutic rescue regimen.

Clinical implications of ZAP-70 expressionin chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a disease with an extremely heterogeneous prognosis. Because of this and because of the lack of a truly effective therapy, treatment of CLL must be adapted to the individual risk of each patient. Over the last quarter of century, prognosis of patients with CLL has been based on clinical features. In the last few years a number of biological prognostic parameters have been identified. Among them, the expression of ZAP‐70 in neoplastic B lymphocytes is increasingly being recognized as of paramount importance to predict outcome. Patients with a low percentage (<20%) of ZAP‐70 positive neoplastic B lymphocytes have a much better prognosis that those with a higher proportion (>20%) of ZAP‐70 positive neoplastic B lymphocytes.