Yuichiro Fukasawa

An AFP-producing gastric carcinoma with features of hepatic differentiation: a case report

A patient with primary gastric adenocarcinoma with extremely high serum alpha‐fetoprotein (AFP) levels (12,000 ng/ml) is described. Histologically, foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Within tumor cells, AFP was identified with both light and electron microscopy, showing the production of AFP by tumor cells themselves. Furthermore, 88% of serum AFP combined with Concanavalin A (ConA), revealing that it was hepatic‐type AFP and not germcell‐type. Localization of alpha‐I‐antitrypsin within tumor cells was also noted. Ultrastructural study showed that there were two types of structures corresponding to periodic acid‐Schiff (PAS)‐positive globules, one of which, the proteinaceous material in intracytoplasmic lumina, was found to contain AFP. Among gastric adenocarcinomas with a high serum AFP level (several thousand or more ng/ml of AFP), foci resembling hepatocellular carcinomas have been reported by several investigators. Those gastric carcinomas, together with the current case, may constitute a clinicopathologic entity, hepatoid adenocarcinoma of the stomach.

Detection of a novel HLA-DQ specificity: serological and immunochemical analyses by a monoclonal antibody

A monoclonal antibody (mAb) with a novel human B-cell allospecificity was produced by immunizing a C3H/He mouse with the human B lymphoblastoid cell line EBV-Wa (HLA-DR4/Dw15/DQblank homozygous). The mAb, termed HU-46, reacted with B cells from not only DR4/Dw15-positive individuals but also certain DRw8/Dw8-positive ones whose DQ phenotypes had not yet been defined. Two-dimensional gel analyses indicated that the mAb recognized class II antigens which were encoded by the HLA-DQ locus. Furthermore, in genetic analysis, the gene encoding the class II antigen detected by HU-46 met the Hardy-Weinberg condition as a fourth allele of the DQ locus. We provisionally labeled this novel DQ specificity DQWa.

Tonsillectomy ameliorates histological damage of recurrent immunoglobulin A nephropathy after kidney transplantation.

Recurrence of immunoglobulin A (IgA) nephropathy (IgAN) after renal transplantation is important as a cause of graft failure under improving rejection control. However, no specific therapy for recurrent IgAN is currently available. In this study, we evaluated the histological efficacy of tonsillectomy for allograft IgAN.

A Study on Class II Antigens Involved in the T Cell Prorliferative Responses to PPD Using Cross-Reacting Monoclonal Antibodies in Human and Murine System

Two monoclonal antibodies (MoAb) 1E4 and ISCR3, which detect class II antigens across species barriers, were studied for their inhibitory effects on human and murine T cell proliferative responses to purified protein derivative of tuberculin (PPD). The 1E4 detected at least a polymorphic determinant on I-A molecules from mice carrying the H-2b haplotype, and the ISCR3 detected the Ia.7 determinant on I-E molecules. Nevertheless, both 1E4 and ISCR3 recognized monomorphic determinants on HLA-DR antigens (human I-E equivalent molecules), but not on HLA-DQ antigens (human I-A equivalent molecules). It was demonstrated that 1E4 significantly inhibited PPD-specific responses of T cells from Ib-bearing mice. In contrast, ISCR3 showed marginal effects on the responses of mice bearing Ia.7. However, in the human system both 1E4 and ISCR3 reduced proliferative responses to PPD. These results suggest that a functional difference exists between humans and mice in the I subregion products involved in the T cell proliferative responses to PPD.

Granulomatous tubulointerstitial nephritis in a renal allograft: three cases report and review of literature

Granulomatous interstitial nephritis (GIN) is a rare histologic diagnosis in renal allografts. We report three cases with GIN. Case 1: a 37‐yr‐old woman received a kidney from her mother. On follow‐up 15 months later, serum creatinine was increased and a graft biopsy showed epithelioid granuloma in the center of massive mononuclear cell infiltration. She had presented with refractory urinary tract infection treated with antibiotics before biopsy. The case was presumed to be GIN associated with UTI or hypersensitivity to medication. Case 2: a 47‐yr‐old woman received a second graft from a non‐heart‐beating donor. A protocol graft biopsy was performed six months after transplantation and showed several granulomatous nodules. She was followed closely without therapy. Case 3: a 27‐yr‐old woman received an ABO‐incompatible kidney from her father. A protocol graft biopsy was performed three months after transplantation and showed granulomatous reaction with severe mononuclear cell infiltration. She received steroid pulse therapy. The two latter patients had no obvious factor contributing to GIN. Therefore, they were presumed to have idiopathic GIN. Infection is considered to be the main causative factor of GIN in renal allografts. This paper describes rare cases of GIN that had no infectious episode in the renal allografts.

Long-term histopathology of allografts in sensitized kidney recipients

Successful desensitization therapy has brought satisfying short‐term outcomes in the recipients with anti‐donor antibody. We analyzed the long‐term pathology of the allografts in the sensitized kidney recipients. Eleven stable recipients after desensitization against positive flow cytometry T‐cell crossmatch (FTXM) were included. They were divided into two groups, based on the protocol biopsies findings at three to eight yr (group 1: subclinical glomerulitis and/or peritubular capillaritis, n = 5 and group 2: no rejection, n = 6). Estimated glomerular filtration rate (eGFR), presence of donor‐specific antibody (DSA), mean channel shift (MCS) of FTXM, urine protein levels, acute antibody‐mediated rejection (AAMR) episodes, and protocol biopsy findings were compared. Chronic transplant glomerulopathy was found in final biopsy of all group 1 cases. DSA was positive in 60% but C4d was positive in 20% case of the group 1. The history of AAMR was only found in the group 1. There was no difference in eGFR decline or proteinuria. The MCS of FTXM was higher in the group 1. The recipients with AAMR history, high MCS in FTXM, and subclinical microvascular inflammation in the early protocol biopsies have risk for developing chronic rejection in long term.

De novo proteinuria with pathological evidence of glomerulonephritis after everolimus induction.

A 68‐year‐old man who underwent living‐unrelated kidney transplantation from his spousal donor was immunosuppressed with tacrolimus and mycophenolate mofetil. Despite his uneventful clinical course, protocol biopsy at 2 years post transplant showed de novo CNI tubulotoxicity despite low tacrolimus exposure. Everolimus was added in order to discontinue TACER. However, prominent proteinuria impeded continuation of everolimus since biopsy showed diffuse glomerular endocapillary proliferation without C4d deposition. No donor‐specific antibody was detected. Pulse steroids were given and proteinuria returned to normal with histological reversal.

A case of progressive thrombotic microangiopathy after ABO-incompatible renal transplantation

Miura M, Fujita H, Suzuki A, Kubota KC, Fukasawa Y, Shimoda N, Tsuchihashi S, Tamaki T. A case of progressive thrombotic microangiopathy after ABO‐incompatible renal transplantation.
Clin Transplant 2011: 25 (Suppl. 23): 19–22.
© 2011 John Wiley & Sons A/S.

Detection of a novel HLA-DQ specificity

At the Ninth International Histocompatibility Workshop (Munich, 1984), DP, DQ, and DR antigens were officially recognized as the class II gene products of the H L A complex (Bodmer et al. 1984). The DP, D Q , and D R loci were considered to have at least 6, 3, and 14 (2 more in a proximal locus) alleles, respectively. DQ molecules have been revealed to be the human homolog of mouse A molecules (Bono and Strominger 1982, Giles et al. 1983), although only three alleles have been identified despite the fact that the mouse A system is highly polymorphic (Klein et al. 1983). Recent findings of twodimensional gel analyses, however, have demonstrated that the D Q system is as polymorphic as the mouse A system (de Kretser et al. 1982, Shackelford et al. 1983, Maeda et al. 1984, Ishikawa et al. 1985). Nevertheless, no serological reagent was available to detect the fine specificity corresponding to these observations, except for a few mouse monoclonal antibodies (mAbs) such as TA10 and HU-23, both of which dissected DQw3 antigens associated with Dw4 and Dw5 from those associated with other D specificities (Kasahara et al. 1983, Maeda 1984). Thus, only three kinds of alloantisera detecting the supertypic determinants on DQ molecules were utilized to define the phenotypes of the DQ antigens as DQwl, w2, and w3. Moreover, the limitation of antisera made it difficult to define the DQ antigens associated with the Dwl5-DR4 and certain Dw8-DRw8 specificities, which do not belong to any of the DQw 1, w2, and w3 families (Schreuder and Degos 1984). To investigate the D Q system, we produced mouse mAb HU-46, which defines a novel DQ specificity,

De novo proliferative glomerulonephritis with monoclonal IgG deposits of the IgG1κ subtype in a kidney allograft.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) has recently been described in cases with glomerular disease. Only 16 cases of recurrent or de novo PGNMID have been reported in the transplanted kidney. Here we report a case of de novo PGNMID in a renal allograft diagnosed in the early stage by protocol biopsy. A 41‐year‐old male with end‐stage kidney disease caused by focal glomerular sclerosis received a living‐related kidney transplant. The post‐transplantation course was stable, except for an early episode of acute T cell‐mediated rejection. Mesangial C1q deposition was found on the 3‐year protocol biopsy. On the 4‐year protocol biopsy, mild mesangioproliferative changes and deposition of IgG, C1q, C3, IgG1, and κ light chain were evident, confirming the diagnosis of PGNMID of the IgG1κ subtype. Furthermore, mild proteinuria was detected at that time. Because a subsequent haematological examination revealed high copy number Epstein–Barr virus (EBV) DNA and free κ light chain in blood, the post‐transplant lymphoproliferative disorder (PTLD) was suspected. Mycophenolate mofetil (MMF) was discontinued and rituximab was administered for the treatment of PTLD; subsequently, the improvement in proteinuria and serum creatinine was found 2 months after rituximab administration.