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A 73-year-old man with a 5-day history of continuous hiccup, fever, and rapidly progressing paraplegia was admitted to our hospital. On admission, he exhibited dysarthria, complete paraplegia, and insentience of both lower limbs. Head and spine MRI showed abnormal, asymmetric lesions in the white matter, basal ganglia, and brainstem, and multiple spinal cord lesions. Test for serum anti-AQP4 antibody was negative. Evaluation of human leukocyte antigen (HLA)-B51 was negative; however, HLA-B54 was positive. Although skin lesions were absent, we considered neuro-Sweet disease and high-dose steroid therapy was initiated. The hiccup disappeared gradually, and he regained the ability to walk with a cane 30 days after the onset. Subsequently, the patient tested positive for serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody. It is important to consider MOG antibody-related disease as potential diagnosis in patients exhibiting clinical features of neuro-Sweet disease except for the absence of skin lesions.

Graft-versus-host disease (GVHD) is a major barrier to successful allogeneic stem cell transplantation. Therefore, the identification of an alternative donor with a lower risk of GVHD is important for patients lacking an HLA-identical sibling donor. To date, HLA studies of large cohorts of unrelated hematopoietic stem cell transplantation (UR-HSCT) have provided important and helpful information for donor selection. In UR-HSCT through Japan Marrow Donor Program, patient and donor HLA-A, -B, and -C, and HLA-DRB1 and -DQB1 double mismatches are significant risk factors for severe GVHD and mortality. HLA-DPB1 mismatch does not affect survival; however, it reduces the chances of leukemia relapse. In the analysis of a specific allele effect on transplant outcomes, HLA-C * 14:02 was significantly associated with an increased risk of severe acute GVHD. The development of next-generation sequencing (NGS) has enabled full-length HLA allele typing. Evolutionary analysis of the entire HLA-DPB1 revealed that a highly conserved region from exon 3 to 3'UTR provoked acute GVHD that was different from a T-cell epitope mismatching algorithm, reflecting exon 2 polymorphisms. Furthermore, a recent study demonstrated the importance of full-length NGS HLA typing on UR-HSCT outcomes. The usage of NGS may provide important information on the implications of the HLA genes in allogeneic stem cell transplantation.

Since the introduction of hematopoietic stem cell transplantation (HSCT), matching the HLA with the donor and recipient is the most important factor in improving the outcome. Currently, we are getting familiar with cord blood transplantation and haplo-identical stem cell transplantation which are beyond HLA disparity. However, even in this era, the significance of HLA for HSCT has not changed, and new technology provides knowledge regarding HLA and HSCT. Usually, HLA typing methods only estimate the allele, but next generation sequencing (NGS) can detect the whole sequence of the HLA gene. Moreover, because the NGS method can be used for quantitative analysis, we can also detect 6pLOH in some disease conditions. Furthermore, a previous report showed that HLA epitope mismatch also influenced the outcome of HSCT. This review shows this new technology and findings on HLA and HSCT.

Graft-versus-host disease (GVHD) caused by patient and donor human leukocyte antigen (HLA) mismatch is a complication of unrelated hematopoietic stem cell transplantation (UR-HSCT) that leads to reduced success rates. To date, studies on HLA alleles in transplant have provided important information on unrelated donor selection. In this study on the effects of specific HLA alleles on acute GVHD in UR-HSCT, HLA-C ＊ 14:02 was found to be significantly associated with an increased risk of acute GVHD. Patient HLA-C ＊ 14:02 and donor HLA-C ＊ 15:02 mismatch was usually KIR2DL-ligand mismatch in the GVH direction in Japanese UR-HSCT cohort, and the higher risk of severe acute GVHD for KIR2DL-ligand mismatch in GVH direction demonstrated in previous Japanese UR-HSCT study was attributable to this particular mismatch combination. Recently, the risk of acute GVHD after UR-HSCT was reported to be associated with the HLA-DP expression level, which is associated with the variant rs9277534 located in the 3'untranslated region (UTR) of the HLA-DPB1 gene. We constructed phylogenetic trees of HLA-DPB1 alleles using next-generation sequencing (NGS) HLA typing data that included introns and 3'UTRs. Results reported that rs9277534 represented a highly conserved region from exon 3 to the 3'UTR, which may lead to acute GVHD via a mechanism different from that observed using T-cell epitope mismatching algorithms, perhaps reflecting exon 2 polymorphisms. The usage of innovative technologies such as NGS in genetic analysis and HLA typing thus has profound implications in this field.

Human leukocyte antigen (HLA) mismatch increases the risk of severe graft-versus-host disease (GVHD) and transplant-related mortality. However, the variety of stem cell sources such as cord blood units or the improvements in GVHD prophylaxis makes the interpretation of HLA mismatch more complex. In unrelated transplantation, the locus of HLA mismatch has a great impact on the donor candidate selection, whereas in related transplantation, it has an impact on the intensity of GVHD prophylaxis because donor availability is limited. Anti-thymocyte globulin and post-transplant cyclophosphamide are attractive GVHD prophylactic agents to reduce the risk of immune-associated complications in HLA-mismatched transplantations. HLA mismatch has a reduced impact in adult cord blood transplantation. In this review article, the impact of HLA mismatch based on graft sources is discussed.

HLA-haploidentical hematopoietic stem cell transplantation from related donors has gained attention as an alternative treatment for patients who do not have HLA-identical siblings and lack the time to search for HLA-matched unrelated donors due to availability for nearly all individuals. As a key factor in the success of this approach is depletion of donor T cells, HLA-haploidentical transplantation has rapidly gained acceptance worldwide with the development of three platforms: 1) CD34-positive cell selection using CliniMACS®; 2) the conditioning regimen with anti-thymocyte globulin; and 3) a recently-developed, post-transplant cyclophosphamide regimen. Since the high efficacy of T-cell-depletion provides both sufficient suppression of GVHD and a high risk of opportunistic infection, there is an urgent need to strengthen the prevention of viral infections. On the other hand, conditioning with ATG and the post-transplant cyclophosphamide regimen are becoming the strategies mainly used in haploidentical transplantation because of high practicability and low risk of infection, though these platforms necessitate other drugs for GVHD prophylaxis due to the low efficacy of T cell depletion. Together with progress in these platforms, outcomes of haploidentical transplantation are comparable to outcomes of HLA-matched transplants. Currently, HLA-haploidentical transplantation is increasingly being recognized as a novel breakthrough in hematopoietic stem cell transplantation.

Cord blood (CB) has been an alternative stem cell source for patients with a wide variety of hematological diseases. When compared with unrelated bone marrow transplantation (u-BMT), obvious advantages of CB are the rapid availability and tolerance of 2 HLA antigen mismatch, which have increased the chances of transplantation for patients who lack a suitable donor or need urgent transplantation. Although higher rates of engraftment failure as compared to other stem cell sources after cord blood transplantation (CBT) have been a serious concern, the mechanisms underlying these failures have gradually been clarified by analyzing accumulated clinical data, thereby contributing to improvement of engraftment. Recent large-scale retrospective comparisons of clinical outcomes between CBT and u-BMT from HLA-matched donors have obtained comparable results, and moreover, results of CBT have been promising even in elderly patients and those in non-remission status. This review describes the current status of CBT and problems to be solved, along with discussion of developing strategies aimed at improving patient outcomes.

In a 72-year-old female, subacute right hemiplegia and aphasia appeared in late May 2011. The results of hematology, a cerebrospinal fluid test, (13)F-FDG-PET, and cephalic MRI suggested intravascular/malignant lymphoma. Brain biopsy was performed. Pathological findings did not suggest a malignant tumor. In the perivascular space, the infiltration of neutrophils or histiocytes was observed. The patient was referred to the Department of Neurology. Based on the results of various examinations, infection was ruled out, and steroid therapy was conducted. Marked improvement was achieved. Subsequently, the results of human leukocyte antigen (HLA) typing showed B54/Cw1. As dermal findings were absent, it was impossible to make a definitive diagnosis of neuro-Sweet disease, but the disorder was regarded as a neuro-neutrophilic disease, which is a more comprehensive entity. Few studies have reported brain tissue findings of active neuro-neutrophilic disease. We report the present case, which will contribute to future research.

Fourteen patients who received allogeneic hematopoietic stem cell transplantation (HSCT) from a serologically HLA one mismatched related donor (MMRD) between November 1987 and July 2003, were compared with HSCT from matched sibling donor (MSD) (n=142) or matched unrelated donor (MUD) (n=78). Cumulative incidence of acute graft-versus-host disease (GVHD) in patients with MMRD was significantly higher than in those with MSD, but was not different from that in those with MUD. There was no difference in the incidence of extensive type chronic GVHD in HSCT according to donor type. Overall survival (OS) at 5-years in patients with MMRD, MSD and MUD was 42.8%, 55.6% and 44.3%, respectively. The presence of acute GVHD and disease status at HSCT were identified as risk factors for overall survival by multivariate analysis. Acute GVHD was a risk factor for prognosis in patients with MSD and MUD, but not in those with MMRD. It was confirmed that the therapeutic results could be obtained in HSCT from MMRD as well as MUD.

The patient was a 53-year-old woman with an 18-year history of recurrent oral aphtae, genital ulcers and folliculitis-like erupsions without mucocutaneus symptoms. She was admitted to our hospital for headache, and presented with meningeal irritation, dysarthria and right pyramidal signs. Brain MRI showed abnormal intensities extending from the right midbrain to the bilateral corona radiata, accompanied by contrast enhancement. She was diagnosed as having an incomplete form of neuro-Behçet disease (NBD) based on the diagnostic criteria for NBD. However, the HLA-type was defined as B54 and Cw1, which is common and specific in neuro-Sweet disease (NSD). Oral administration of prednisolone was markedly effective for the neurological symptoms and improved radiological findings, suggesting NSD rather than NBD as the clinical diagnosis for this patient Since she presented with clinical features that appeared in both diseases, the definitive diagnosis was clinically difficult. While tapering the dosage of prednisolone, we carefully observed the appearance of skin lesions and erythema nodosum appearing on her right lower leg. Skin biopsy demonstrated the features of erythema nodosum: lobular panniculitis with the accumulation of neutrophils and lymphocytes with necrotic fatty cells in the subcutaneous area, which was compatible with skin lesions in NBD. In our case, pathological findings of the skin lesion were required to differentiate between NBD and NSD, indicating the need for careful follow-up of dermatologic signs appearing in such a case.

A 4-year-old girl with familial hemophagocytic lymphohistiocytosis (FHL) underwent unrelated cord blood stem cell transplantation (uCBSCT) using the fludarabine-based non-myeloablative conditioning regimen. Shortly after the uCBSCT, she experienced the reactivation of the FHL, and subsequent graft failure. Considering that the residual recipient lymphocytes, which survived after non-myeloablative conditioning, had a role in the FHL reactivation and in the graft rejection, myeloablative conditioning combined with horse ATG was used to eradicate the recipient lymphocytes in the second CBSCT. Furthermore, in order to prevent rejection, cord blood, the DNA type of which was completely matched in a host to graft (HVG) direction, was selected. In the second uCBSCT, FHL reactivation was noted at a limited level. Complete chimerism was achieved and the NK-cell activity recovered to the normal range. Our case suggests the necessity of the conditioning regimen to eradicate host lymphocytes in the stem cell transplantation for FHL, and the significance of HLA DNA-typing in uCBSCT for pediatric patients.

A 44-year-old man with relapsed acute promyelocytic leukemia (APL), refractory to all-trans-retinoic acid (ATRA), daunorubicin, and cytosine arabinoside, was treated with arsenic trioxide (ATO). ATO was given intravenously at a dose of 0.15 mg/kg/day for 20 days, and the patient achieved complete remission. No serious adverse events related to ATO infusion were observed. He received ATO for 10 days as consolidation therapy and subsequently underwent HLA-matched unrelated donor stem cell transplantation. He remains in molecular remission 10 months after transplant. This case suggests that ATO could be a useful therapy prior to allogeneic stem cell transplantation in relapsed APL.

Bone marrow transplantation(BMT) from genotypically human leukocyte antigen (HLA)-matched siblings improves long-term survival in patients with hematologic malignancies. However, more than 70% of patients who could benefit from allogeneic BMT do not have a matched sibling donor. Furthermore, allogeneic BMT has been limited to young patients because of the increased risk for regimen-related toxicity and graft-versus-host disease(GVHD) that occurs with increasing age. HLA-haploidentical minitransplantation may solve these problems. In minitransplants using a preconditioning regimen consisting of fludarabine, busulfan and anti-T-lymphocyte globulin and a GVHD prophylaxis of tacrolimus and methylprednisolone, we showed that minitransplantation from HLA-haploidentical related donors was possible.

Over the last two decades, four major therapeutic approaches have dramatically changed the prognosis in chronic myelogenous leukemia(CML). Those include allogeneic stem cell transplantation, interferon-alpha based regimen, donor-leukocyte infusions, and the revolutionary BCR/ABL tyrosine kinase inhibitor such as STI571. Each modality has exploited and targeted different aspects of CML biology, and is associated with different risk-benefit ratios. In this section, we update the results of both related and unrelated donor transplantation, donor lymphocyte infusions, and non-myeloablative stem cell transplantation in CML in comparison with the other treatment modalities.

We describe a 46-year-old HLA-homozygous female patient with CML who received a bone marrow transplant from her son, who had two HLA (A, B) loci mismatch. After conditioning with total body irradiation plus cyclophosphamide, the patient received 4.8 x 10(8) bone marrow cells/kg. Cyclosporin and short-term methotrexate were used for GVHD prophylaxis. She successfully established rapid engraftment with no acute GVHD, and later developed chronic but mild GVHD. Family members with two HLA loci mismatch may be considered as candidate donors for "hetero to homo" bone marrow transplantation.

We performed an HLA-mismatched T cell non-depleted bone marrow transplant on a 53-year-old man with acute erythroleukemia that was highly resistant to conventional remission-induction chemotherapy. After conditioning that included total body irradiation, the patient received a two-HLA-antigen-mismatched bone marrow graft harvested from his sister using tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. He successfully established rapid engraftment accompanied by steroid-responsive GVHD localized to the skin. Although bone marrow samples on day 31 and day 66 disclosed a complete remission with full donor chimerism, the patient relapsed and died of pulmonary infection on day 154. There is evidence that tacrolimus is effective in alleviating GVHD. Selected patients who have partially mismatched related donors with less HLA disparity may benefit from tacrolimus-based T cell non-depleted bone marrow transplants because of the more potent graft-versus-leukemia effect that can be expected compared to transplants using T cell depleted inoculum.

Thirty-five children with poor-prognosis disease underwent allogeneic bone marrow transplantation (BMT) from related donors other than HLA identical siblings (parents in 18 cases, non-identical siblings in 14, and other relatives in 3). Phenotypically identical donors were involved in 12 cases, donors with one mismatched locus in 17, and donors with two or more mismatched loci in 6. Thirty-two of the children received total-body irradiation as part of their conditioning regimen, followed by unpurged marrow-cell infusions (averaging 4.09 x 10(8) cells/kg). Methotrexate and cyclosporin were administered for graft-versus-host disease (GVHD) prophylaxis; 15 of the children also received antithymocyte globulin (ATG) infusions. The effective graft rate for the group was 84. 8%; of 5 patients who experienced rejections, 4 had non-malignant diseases. The incidence of grade II-IV acute GVHD was 48.4%, significantly higher than that for groups that received allogeneic BMT from matched sibling donors. Three children (8.8%) died of severe GVHD. The incidence of acute GVHD in phenotypically matched patients was the same as that in the one-locus mismatched cases. MLC reactivity affected the incidence of acute GVHD (60.0% MLC-positive, 28.6% negative). ATG reduced the severity of acute GVHD. The event-free survival rate was 40.8 +/- 8.5% for the entire group (N = 35; 32.9 +/- 10.5% for the 22 children with malignancies, and 53.8 +/- 13.8% for the 13 with non-malignant diseases). Despite the risk of severe GVHD, allogeneic BMT from related donors other than HLA-identical siblings seems to be an effective treatment for patients with poor-prognosis diseases.

Eleven leukemia patients who had undergone bone marrow transplants from HLA-A, B, DR genotypically mismatched unrelated donors received FK506 and short-term methotrexate as prophylaxis for graft-versus-host disease (GVHD). Grade III-IV acute GVHD developed in 2 of the patients, and chronic GVHD developed in 4 of the other patients. Adverse drug reaction included reversible nephrotoxicity, hyperglycemia (all patients) and hypertension (9 patients). Hyperglycemia and hypertension of grade 3 or higher occurred mostly in the patients who were on supplemental steroids. However, severe nephrotoxicity was not observed. Complications included cystitis (4 patients), cytomegalovirus colitis (3 patients), Interstitial Pneumonitis (IP) (3 patients), tuberculosis (1 patient), and thrombotic microangiopathy (1 patient). None of patients relapsed. Although close monitoring of FK506 blood concentration and patient clinical signs are required, we concluded that FK506 is effective for GVHD prophylaxis after bone marrow transplantation from HLA-A, B, DR genotypically mismatched unrelated donors, and that adverse reactions due to FK506 are controllable. To determine the long-term effectiveness of this drug, it will be necessary to conduct prospective randomized studies that compare it wiht cycloporin A as a preventive treatment against GVHD in patients who receive bone marrow transplants from HLA genotypically mismatched unrelated donors.

A statistic survey was made on the clinical results of living and cadaveric renal transplantations performed at our department between October 1980 and June 1996. A total of 38 patients received 6 living and 32 cadaveric renal transplants. The graft and patient survival rates of a living renal transplantation were 83.3% and 100% at 3 years, respectively. The graft survival rate of cadaveric renal transplantation was 66.3% at 3 years and 56.0% at 5 years. In a cadaveric renal transplantation, patients with episodes of acute rejection within 12 months showed a significantly worse graft survival rate. This clinical parameter seems to be a prognostic factor for a long-term graft survival.

Allogeneic bone marrow transplantation (BMT) can cure some hematologic and solid malignancies, but its success depends on the prompt identification of a suitable donor and the avoidance of severe graft-versus-host (GVH) disease. Transplantation using hematopoietic stem cells from umbilical cord blood may overcome these problems. Over the past several years, cord blood transplantation (CBST) from siblings and unrelated donors has been performed in more than 300 patients. The probability of event-free survival was almost similar to that for BMT. This review described the recent status of CBST in USA, Europe and Japan, and the outlook for CBST.

The Japan Marrow Donor Program (JMDP) was established in 1992, and managed by the Japan Marrow Donor Foundation and the bone marrow data centers which are affiliated with the Japanese Red Cross. Since 1992, about 82,000 donors and 4,400 patients have been registered. HLA typing of registered donors is performed 2 steps. Serological HLA-A, -B locus typing and low-resolution HLA-DRB1 locus DNA typing are performed at the donor data centers. For the final matching test, serological HLA-A, -B locus typing is performed as reconfirmation and high-resolution HLA-DRB1 DNA typing are performed. The class I DNA typing is performed for A2, A26, B39 and B61. These antigens occur with a high frequency and each can be subtyped into more than three alleles in Japanese. A retrospective study on the effect of matching or mismatching HLA class I and class II alleles between the donor and recipient on the survival rate of 363 transplanted is currently being performed using JMDP samples. In the report of this research project supported by the Ministry of Health and Welfare matching HLA-A, -B locus alleles of donor and recipient decreased the risk of acute GVHD and improved survival after unrelated marrow transplantation.

A 9-year-old with chronic myelogenous leukemia (CML) who received bone marrow transplantation from an unrelated donor (UBMT), is reported. He also suffered from congenital heart disease (CHD) consisting of corrected transposition of the great arteries and dextrocardia. The cardiac output was within normal limits. The conditioning regimen included busulfan, melphalan, ALG and TLI. Cyclophosphamide was not used because of it cardiotoxicity. The HLA-phenotype of the donor was identical with that of the patient. DNA typing showed was haplodentical DRB1. The patient is alive 18 months after the UBMT. This case showed that UBMT was possible in a CML patient with CHD, without congestive heart failure.

Remarkable clinical effectiveness of leukapheresis (LP) using a cotton-wool filter as a therapy for patients with rheumatoid arthritis (RA) was previously reported. To study the mechanism and indications for this therapy, 14 patients with RA were treated with this filter 6 times at 2 weeks intervals. The effects on clinical symptoms and subpopulations of peripheral blood mononuclear cells were evaluated on day 0, 3, 7, 14, 42 and 84. The Ritchie articular index, swollen joint counts, Lansbury index and health assessment questionnaire (HAQ), all showed improvements within the first week and the improvements were still observed 3 month later. Improvements in tender joint counts and visual analog pain scale (VAPS) were also observed on day 84. Eight patients showed remarkable improvements (responders) and 6 showed no apparent improvement (non-responders) according to the ACR core set criteria. Responders showed several characteristic features compared to non-responders as follows: the duration of RA was significantly shorter, the anatomical stage was earlier, the positive rate of susceptible HLA-DR4 haplotype associated with Japanese RA (DRB1*0405) was lower, and the proportion of CD4 + Leu8 + lymphocytes and the ratio of CD4+ cells to CD8+ cells (CD+/CD8 ratio) in the peripheral blood were higher throughout the treatment period and increased further even after the course of therapy. The proportion of CD4 + Leu8 + cells was inversely correlated with HAQ and VAPS, suggested that it is critically involved in the mechanism of this therapy. Blood leukocyte analysis at inlet and outlet of the filter showed increase of CD4 +, CD4 + Leu8 + cell percentages and CD4/CD8 ratio. These results suggested that patients with a shorter disease duration, less destruction of the joint, and without susceptible genes were more responsive to this therapy and that the mechanism of clinical improvement of RA by LP with cotton-wool involves immunological modification, such as immunosuppression by CD4 + Leu8 + lymphocytes.

Placental and umbilical cord blood, as an alternative course of haematopoietic stem cells for bone marrow reconstitution, have recently been showed to yield successful sibling-donor cord blood grafts children. The advantages of using cord blood are related to the high number of haematopoietic progenitors in circulation at birth. In our study there was a remarkable heterogeneity of volume, number of nucleated cells and the number of progenitors from sample to sample. Seven out of 40 samples of more than 61 ml blood volume contained 1.8 (+/- 1.0) x 10(5) CFU-GM or 6.0 (+/- 4.8) x 10(8) nucleated cells. 10 ml of whole blood was necessary for laboratory tests including ABO blood type, screening of infectious markers, HLA typing, as well as frozen sera and cells for the possible future tests. Collected cord blood of more than 70ml in volume may have sufficient numbers of CFU-GM for engraftment to pediatric patients weighing about 20 kg. A cord blood bank project is now going on by collecting blood with informed consent of the mother in cooperation with obstetrics and gynecology staff.

To reveal immunogenetic factors involved in the pathogenesis of metal allergy, 30 unrelated Japanese patients with histories of metal allergy were typed for HLA. They were confirmed by an unequivocal positive patch-test reaction to mercury, nickel or palladium. The HLA-DR and -DQ DNA were typed by using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) method. The frequency of each allele in the patient groups was compared to that in normal Japanese subjects. In mercury sensitive patients, there was no significant HLA association. In nickel sensitive patients, there was a significant increase of DRB4 (p < 0.05) but no significant association of DRB1 nor DQ locus, although there was an increase of DRB1*0405 (R.R = 2.36). In palladium sensitive patients, there were significant increases of DRB4 (R.R. = 15.48, p < 0.05), DR4(R.R. = 13.27, p < 0.005), DRB1*0405(R.R. = 4.43, p < 0.05), and DQB1*0401 (R.R. = 4.59, p < 0.05), and significant decreases of DRB5 (R.R. = 0.09, p < 0.05), and DQA1*0103 (R.R. = 0, p < 0.05).

In order to examine the clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis, we analyzed clinical features and HLA typing of 85 patients in a multicenter study. Eighty-five patients with secondary amyloidosis associated RA were studied. The diagnosis of secondary amyloidosis were made on histological findings by biopsy or autopsy. The most common biopsy site was gastrointestinal tract (79.5%). Clinical symptom and the frequency at the time of diagnosis were; diarrhea (35 cases), abdominal pain (22 cases) and vomiting and nausea (16 cases). Abnormalities and the frequency in a laboratory test included proteinuria (49 cases), increased serum creatinine (32 cases), anemia (30 cases) and hematuria (15 cases). Twenty-eight patients were dead and 57 patients were alive at the time of the study. The average duration between diagnosis of amyloidosis and death was 19.4 +/- 18.5 (SD) months among the dead patients. The average duration after diagnosis of amyloidosis was 24.2 +/- 19.5 (SD) months in surviving patients. The causes of death were renal failure complicated with heart failure (6 patients), heart failure alone (3 patients) and renal failure alone (2 patients). Fifty-nine patients in the control group who were negative to amyloid deposition on biopsies at more than one site in the gastrointestinal tract, were clinically compared with patients in the amyloidosis group. No difference were noted in the age of RA occurrence and the stage between the two groups. As to the class, however, the number of patients with severe functional disorder (class 3 or severe) was larger in the amyloidosis group. There were no significant difference between the two groups in Lansbury's activity index. On hematology, biochemistry and urinalysis, the incidences of increased white blood cell count, anemia, increased platelet count, increased serum creatinine, hypoproteinemia, hypoalbuminemia, increased IgA, and increased urine and blood BMG were statistically significantly higher in the amyloidosis group than in the control group. HLA-A, -B, -C, and DR-locus antigens were compared in the 53 patients in the amyloidosis group and in the 59 subjects in the control group. There were no significant differences in frequency of HLA-A, and -B antigens between two groups. Frequency of CW7 antigen was significantly decreased in the amyloidosis group (13.2%) than in the control group (39.0%). Frequency of DR1 antigen was decreased in the amyloidosis group (3.8%) than in the control group (22.0%), although the difference was not significant. These findings suggest the possible involvement of genetic factors in the occurrence of amyloidosis. It is suggested that the occurrence of amyloidosis is suppressed by some genes which are linked with CW7 antigen.

This report described 45-year-old identical twin sisters with IgA nephropathy. Case 1 presented with microscopic hematuria and proteinuria at the age of 39. Case 2 was found proteinuria at the age of 32. Both the physical examination and laboratory data of these cases were normal. Serum level of IgA was not elevated. The renal biopsy specimen of two cases showed slight mesangial proliferation by light microscopy and mesangial IgA deposition by immunofluorescence microscopy. Their serotype for HLA was found to be HLA-A2, A24, Bw35, Cw1, Cw3, DRw8, DRw12. Several reports indicated the familial occurrence of patients with IgA nephropathy and a strong association with HLA-Bw35 in those patients. The present cases also suggested that an abnormal immune response-linked HLA system may be involved in the development of IgA nephropathy.