The concept that HLA antibodies are specific for epitopes rather than HLA antigens is important not only for the determination of mismatch acceptability for sensitized patients but also for a better understanding of the antibody response to an HLA mismatch. Numerous publications describe epitope-specific antibodies, but there is no standardized information about the repertoire of clinically relevant HLA epitopes. Under auspices of the 16th IHIW, we have developed a website-based registry of antibody-verified HLA epitopes. Epitope notations are based on HLA molecular modelling of amino acid residues in polymorphic sequence positions. Informative epitope-specific antibodies had been induced by a transplant, transfusion or pregnancy and were monoclonal antibodies or eluates of sera absorbed with single HLA alleles. Antibody reactivity was determined in binding assays with single-allele panels. Antibody producer/immunizer HLA types enhanced the characterization of specific epitopes. The Registry also includes epitopes described in original research publications. Based on the extent of antibody reactivity information, we assigned epitope status as confirmed (well documented) or provisional (more data are needed). At present, the Registry has 69 HLA-ABC, 53 DRB1/3/4/5, 17 DQ, 8 DP and 22 MICA antibody-verified epitopes and will be updated on a quarterly basis. Laboratories worldwide continue to submit data about previously unreported antibody-specific epitopes. For each epitope, the website shows its amino acid composition and HLA alleles that share the epitope. Links show antibody reactivity patterns, sensitization information and references. Other links show molecular modelling of corresponding structural epitopes and polymorphic residue information for epitope-carrying alleles. The website will also have a link to epitope frequency information in different populations. Search functions will list mismatched epitopes on mismatched alleles for selected HLA types. The HLA Epitope Registry will become a valuable resource for researchers interested in HLA compatibility at the epitope level and investigating antibody responses to HLA mismatches.

Glomerular podocytes are known to regulate proteinuria and podocyturia correlated with proteinuria. Podocyturia, the urinary excretion of viable podocytes (glomerular epithelial cells), has been associated with proteinuria in preeclampsia. This study is the first to investigate the time course alterations of podocyturia in patients with preeclampsia (11 cases) and normotensive pregnant women (45 cases). Urinalysis was performed at 35 weeks of gestation, 4 days after delivery, and 1 month after delivery. In patients with preeclampsia, podocyturia was evident at 35 weeks of gestation and 4 days after delivery, while proteinuria had already decreased at 4 days after delivery. At 1 month after delivery, almost no patients exhibited podocyturia. In control cases, proteinuria was not significant throughout the study period. However, 9 of the 45 controls exhibited transient and mild podocyturia at 4 days after delivery without proteinuria or hypertension. Statistics indicated a correlation between urinary podocyte number and blood pressure, but not with proteinuria. In conclusion, podocyturia in preeclampsia is transient and almost synchronous with heavy proteinuria. The results suggest that acute podocyte loss implicates podocyturia as the possible mechanism of proteinuria in women with preeclampsia.

In kidney transplantation, the multilayering of the peritubular capillary basement membrane (MLPTC) in electron microscopy (EM) has been recognized as a feature of chronic rejection (CR). In this study, thickening of the peritubular capillary (PTC) basement membrane was evaluated by light microscopy (LM) to determine whether it corresponds to the MLPTC in EM and whether it can be used as a diagnostic marker of CR. Forty-eight patients with late renal allograft were divided into chronic allograft nephropathy (CAN) with CR (Group 1, n = 23), CAN without CR (Group 2, n = 19) and CAN-free (Group 3, n = 6). The thickening of the PTC basement membrane (ptcbm) was scored from grades 0 to 2 (ptcbm score), and the MLPTC thickness was measured in EM. Interobserver agreement on ptcbm scores was statistically significant (Kappa coefficient = 0.63). LM and EM lesions corresponded very well. The ptcbm score was highest in Group 1, and ptcbm2 corresponded closely with CR. Group 1 showed significantly thicker MLPTC than Groups 2 and 3. The results validated the usefulness of the ptcbm score and suggested that the thickening of the PTC basement membrane can be a novel diagnostic marker of CR.

Peritubular capillary basement membrane multilayering (PTCBMML) is a pathological landmark of chronic rejection-induced transplant capillaropathy (TC), but its cellular mechanisms are not fully understood. We observed de novo caveolae formation in endothelial cells in TC under electron microscopy. To examine the role of caveolae and their structural components in TC, biopsy samples from cases of chronic rejection were double-immunostained for Caveolin-1 (Cav-1) and Pathologische Anatomie Leidenendothelium (PAL-E; a marker of peritubular capillary [PC]). Thirty-two cases of chronic rejection (group I) were compared with 18 cases of interstitial fibrosis and tubular atrophy with no evidence of any specific etiology (IF/TA; group II) and eight cases of peritubular capillaritis (group III). The Cav-1/PAL-E immunoreactivities in groups I-III (%Cav-1/PAL-E) were 41.8 ± 23.1%, 8.1 ± 7.3% (p < 0.01 vs. group I) and 12.7 ± 7.4% (p < 0.01 vs. group I), respectively. Furthermore, multiple linear regression models demonstrated that %Cav-1/PAL-E was independently associated with the PTCBMML grade and reduced PC number. No correlation was observed between %Cav-1/PAL-E and PC C4d deposition in group I. We conclude that de novo caveolae formation in PC endothelia is involved in TC in chronic rejection.

An autopsy case of carcinosarcoma of the liver producing granulocyte-colony stimulating factor (G-CSF) is reported. The patient, a 74-year-old Japanese man, presented with multiple liver masses. His serum G-CSF was elevated to 286 pg/mL and a marked leukocytosis of 19 100/microL was observed. The patient had a rapidly aggravated clinical course and died 57 days after admission. Autopsy revealed a liver carcinosarcoma composed both of hepatocellular carcinoma (HCC) and sarcomatous elements immunoreactive with alpha-smooth muscle actin and desmin. Immunohistochemistry revealed positive staining of G-CSF in the cytoplasm of HCC, whereas none of the spindle cells was positively stained. Production of G-CSF was also confirmed by enzyme-linked immunosorbent assay, using the frozen tumor tissue taken at the autopsy. Similar to the majority of G-CSF-producing tumors in the literature, only the epithelial elements of the present case were immunopositive for G-CSF. Although a monoclonal origin of carcinosarcomas has generally been proposed, heterologous differentiation from a single clone might lead to the production of G-CSF only in the epithelial element in the present case. It is suggested that G-CSF was associated with the high-grade transformation of the epithelial elements, as well as the reported phenomenon of conventional HCC producing G-CSF.