Significance of C4d Banff scores in early protocol biopsies of kidney transplant recipients with preformed donor-specific antibodies (DSA).

The significance of C4d-Banff scores in protocol biopsies of kidney transplant recipients with preformed donor-specific antibodies (DSA) has not been determined. We reviewed 157 protocol biopsies from 80 DSA+ patients obtained at 3 months and 1 year post-transplant. The C4d Banff scores (1,2,3) were associated with significant increments of microcirculation inflammation (MI) at both 3 months and 1 year post-transplant, worse transplant glomerulopathy and higher class II DSA-MFI (p < 0.01). Minimal-C4d had injury intermediate between negative and focal, while focal and diffuse-C4d had the same degree of microvascular injury. A total of 54% of patients had variation of C4d score between 3 months and 1 year post-transplant. Cumulative (3 month + 1 year) C4d scores correlated with long-term renal function worsening (p = 0.006). However, C4d staining was not a sensitive indicator of parenchymal disease, 55% of C4d-negative biopsies having evidence of concomitant MI. Multivariate analysis demonstrated that the presence of MI and class II DSA at 3 months were associated with a fourfold increased risk of progression to chronic antibody-mediated rejection independently of C4d (p < 0.05). In conclusion, the substantial fluctuation of C4d status in the first year post-transplant reflects a dynamic humoral process. However, C4d may not be a sufficiently sensitive indicator of activity, MI and DSA being more robust predictors of bad outcome.

Increased TIA1-expressing intraepithelial lymphocytes in cow's milk protein intolerance.

BACKGROUND: Although a high level of intraepithelial lymphocytes (IELs) has been demonstrated in intestinal biopsies from children with cow's milk protein intolerance (CMPI), the properties of IELs in food-sensitive enteropathies remain unclear. In the present study, we analyzed the cytotoxic potential of IELs in CMPI, using a monoclonal antibody directed against the cytotoxic granule-associated protein TIA1. METHODS: The study included 18 duodenal biopsies from 10 children previously diagnosed with CMPI and on a cow's milk-free diet of various duration. Six normal duodenal biopsies from children free of food intolerance served as controls. Immunostaining of formalin-fixed tissues was used to determine in the intraepithelial compartment (1) the number of TIA1-expressing cells per 100 epithelial cells, (2) the number of IELs per 100 epithelial cells, (3) the ratio of TIA1-expressing IELs (TIA1/IEL ratio). RESULTS: In CMPI, the number of IELs and TIA1-positive cells, as well as the TIA1/IEL ratio was significantly increased compared with controls. Moreover, a negative correlation between the TIA1/IEL ratio and the duration of the diet was observed. CONCLUSIONS: These results suggest that the recruitment of IELs with cytotoxic potential is increased in CMPI, and that IEL-mediated cytotoxicity could be involved in the pathogenesis of the disease.

[Cryoglobulinemia]. / Les Cryoglobulinémies.

Cryoglobulinaemias contain seric immunoglobulins which precipitate at low temperatures in some tissues. Based on immunohistochemical analysis of their components (monoclonal or polyclonal), 3 types of cryoglobulinaemias have been identified, and a classification has been proposed. The presence of a paraprotein within the cryoglobulinaemia is due to the proliferation of B cells. Type I is mainly associated with a lymphoproliferative syndrome (myeloma and others...) whereas type II (mixed cryoglobulinaemia) and type III are the result of viral and bacterial infectious diseases, and of autoimmune diseases. Over the last few years, infection by hepatitis C has been found in more than 90% of types II and III cryoglobulinaemias. Cryoprecipitates are pathogenic for kidneys, skin and nervous tissues. In some organs, they are responsible for specific histological lesions, such as necrotizing angeitis with vascular microthrombosis. In kidneys, they occur as endocapillary proliferative glomerulonephrites, accompanied by precipitation of immunoglobulins in the form of intracapillary thrombi. Precipitated immunoglobulins can be identified on frozen specimens. Ultrastructural studies confirm the fibrillar aspect which is characteristic of the cryoprecipitate.