Moyamoya Disease Associated with a Deficiency of Complement Component 6.

Objectives: Complement component 6 (C6) deficiency is a very rare genetic defect that leads to significantly diminished synthesis, secretion, or function of C6. In the current report, we demonstrate a previously undescribed, homozygous missense mutation in exon 17 of the C6 gene (c.2545A>G p.

Disseminated gonococcal infection in a Japanese man with complement 7 deficiency with compound heterozygous variants: A case report.

Rationale: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants.

Patient Concerns: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever.

Proposed criterion for distinguishing ABO mosaics from ABO chimeras using flow cytometric analysis.

Differentiation of ABO mosaics from chimeras is performed using flow cytometry (FCM) analysis. Although mosaics and chimeras have been distinguished by presence or absence of clear resolution using FCM analysis, the lack of quantitative metrics and definitive criteria for this differentiation has made some cases difficult to differentiate. In this study, therefore, we attempted to establish a definitive and quantitative criterion for this differentiation.

A case of neonatal alloimmune thrombocytopenia in the presence of both anti-HPA-4b and anti-HPA-5b antibody: clinical and serological analysis of the subsequent pregnancy.

Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies raised against fetal platelet antigens inherited from the paternal parent. In contrast to Caucasians, in Asians, predominantly in Japanese, most frequently detected antibodies in NAIT are anti-HPA-4b and anti-HPA-5b. In some NAIT cases multiple alloantibodies are detected.

Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans.

CD4(+) Treg cells expressing the transcription factor FOXP3 (forkhead box P3) are abundant in tumor tissues and appear to hinder the induction of effective antitumor immunity. A substantial number of T cells, including Treg cells, in tumor tissues and peripheral blood express C-C chemokine receptor 4 (CCR4). Here we show that CCR4 was specifically expressed by a subset of terminally differentiated and most suppressive CD45RA(-)FOXP3(hi)CD4(+) Treg cells [designated effector Treg (eTreg) cells], but not by CD45RA(+)FOXP3(lo)CD4(+) naive Treg cells, in peripheral blood of healthy individuals and cancer patients.

Detection of anti-human platelet antibodies against integrin α2β1 using cell lines.

Background: Antibodies against human platelet antigens (HPA) are a cause of thrombocytopenia. Detection of rare anti-HPA antibodies using platelet preparations is difficult and would be improved by an alternative method that does not require platelets. In the present study, we describe the establishment of cell lines that stably express specific HPA associated with integrin α2β1 and the application of these cell lines for detecting anti-HPA-5a and anti-HPA-5b antibodies.

Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma.

We expanded CTL specific for Tax (a human T-lymphotropic virus type-1-encoded gene product) in vitro from PBMC of several adult T-cell leukemia/lymphoma (ATL) patients, and document its potential significance as a target for ATL immunotherapy. Tax-specific CTL responses against tumor cells were restricted by Tax-expression and the appropriate human leukocyte antigen (HLA) type. Tax-specific CTL recognized HLA/Tax-peptide complexes on autologous ATL cells, even when their Tax expression was so low that it could only be detected by RT-PCR but not by flow cytometry.

Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an intractable hematologic malignancy caused by human T-lymphotropic virus type 1 (HTLV-1), which infects approximately 20 million people worldwide. Here, we have explored the possible expression of cancer/testis (CT) antigens by ATLL cells, as CT antigens are widely recognized as ideal targets of cancer immunotherapy against solid tumors. A high percentage (87.

The first two cases of neonatal alloimmune thrombocytopenia associated with the low-frequency platelet antigen HPA-21bw (Nos) in Japan.

Background: Neonatal alloimmune thrombocytopenia (NAIT) is a disorder characterized by maternal alloimmunization against paternal fetal platelet antigens. Two healthy, unrelated Japanese women each gave birth to a child with severe NAIT.

Study Design And Methods: To elucidate the maternal causes of NAIT, we conducted serologic and genetic studies in these two NAIT infants.

Distribution of OCA2∗481Thr and OCA2∗615Arg, associated with hypopigmentation, in several additional populations.

Two mutants, OCA2∗481Thr (c.1441G>A, p.Ala481Thr) and OCA2∗615Arg (c.

A Japanese-specific allele in the GALNT11 gene.

In this study, five single nucleotide polymorphisms (SNPs) in the ABCC4, FBN1, CEP152, ZNF804B, and GALNT11 genes were investigated to assess allele frequencies in 14 different populations by a novel pentaplex PCR method. All SNPs were polymorphic in East Asians, whereas mutant alleles were absent or rare in non-East Asians. The frequencies of a mutant allele in FBN1 (rs140598) showed a north-south downward cline in East Asia, whereas those of a mutant allele in ZNF804B (rs1916830) were relatively uniform in East Asia.

Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen-7.

Background: Neonatal alloimmune thrombocytopenia (NAIT) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet (PLT) antigens inherited from the father. A healthy 30-year-old Japanese woman (Hit) gave birth to her second child after an uneventful pregnancy. Nine hours after birth, the infant presented with severe petechiae and a PLT count of 6 x 10(9)/L.

A hypervariable STR polymorphism in the complement factor I (CFI) gene: Asian-specific alleles.

In this study, a short tandem repeat (STR) polymorphism in intron 7 of the human complement factor I (CFI) gene was studied in 637 DNA samples obtained from African, German, Thai, and Japanese populations and German and Japanese families. A total of 41 alleles were observed and classified into two groups, L and H, based on size differences. Group H, which consisted of 16 alleles, was observed only in Thai and Japanese populations at frequencies of 0.

HERC1 polymorphisms: population-specific variations in haplotype composition.

Human HERC1 is one of six HERC proteins and may play an important role in intracellular membrane trafficking. The human HERC1 gene is suggested to have been affected by local positive selection. To assess the global frequency distributions of coding and non-coding single nucleotide polymorphisms (SNPs) in the HERC1 gene, we developed a new simultaneous genotyping method for four SNPs, and applied this method to investigate 1213 individuals from 12 global populations.

Haplotypes in the 5'-upstream region, exons 3 and 4, and introns 2 and 3 of the ABO blood group gene.

We previously described two haplotypes named the ABORR*L-associated and ABORR*S-associated haplotypes in the 5'-upstream region of the ABO blood group gene. Here we studied polymorphisms in exons (Exs) 3 and 4 and introns (Ints) 2 and 3 of the ABO gene, and analyzed the haplotypes in those Exs, Ints, and the 5'-upstream region. Two haplotypes (at Int2nt108-Int2nt362-Int2nt369-Int2nt539-Ex3nt106-Int3nt1178-Int3nt1357-Ex4nt188-Ex4nt189) were deduced to be (1) A-C-C-C-T-C-T-A-T, which was linked with ABORR*L and ABO*O(A), and (2) A-C-C-C-G-T-C-G-C, G-C-C-C-G-T-C-G-C, and A-T-G-A-G-T-C-G-C, which were linked with ABORR*S and the other common ABO alleles.

Typing of the nt343C>T (R95X) allele of the C9 gene by PCR-SSP and the allele frequency of R95X in five ethnic populations.

One of the alleles which leads to ninth component of complement deficiency (C9D) is R95X (nt343C>T), which is present in most cases of C9D in Japan. In this study, we carried out nt343C>T typing by the method of polymerase chain reaction with sequence-specific primers (PCR-SSP), and showed the frequency of the R95X allele in German, Italian, Thai, Korean and Chinese populations. We did not find the R95X allele in the German or Italian populations.

Rare alleles of the ABO blood group system in two European populations.

We performed genotyping of the ABO system in Italian and Israeli population samples. The nucleotides at 11 positions, nts 261, 297, 467, 526, 646, 681, 703, 796, 802, 803 and 1060, were analyzed by PCR-RFLP, PCR-SSP and PCR direct sequencing methods. We found three rare ABO alleles besides the common alleles (*)A1(Pro) (=(*)A101), (*)A2(Leu) (=(*)A201), (*)B (=(*)B101), (*)O(T) (=(*)O01), (*)O(A) (=(*)O02) and (*)O2 (=(*)O03), but did not detect ( *)A1(Leu) (=( *)A102) which is a common allele in Asians.

Molecular basis of complement factor I (CFI) polymorphism: one of two polymorphic suballeles responsible for CFI A is Japanese-specific.

Isoelectric focusing has revealed that human complement factor I (CFI) is controlled by two polymorphic alleles, CFI(*)A and CFI(*)B, and a few rare variant alleles. In this study the molecular basis of the CFI polymorphism was investigated in 174 Japanese. The CFI(*)A was divided into two suballeles, CFI(*)As (R201S) and CFI(*)Ah (R406H).

Possible involvement of heparin-binding protein in transfusion-related acute lung injury.

Background: In antibody-mediated nonhemolytic transfusion reactions, transfusion-related acute lung injury (TRALI) tends to occur typically within 2 hours after a blood transfusion. White cell antibodies or immune complexes have been frequently shown to be associated with the syndrome, although the mechanisms by which they induce TRALI are poorly understood. The aim of this study was to characterize soluble mediators that are released from cells at an early stage after immune stimulation.

DNA polymorphisms and haplotypes in the 5'-upstream region of the ABO blood group gene.

We investigated the polymorphisms in the 5'-upstream region between nucleotide position (nt) -9600 and nt-4105 of the ABO blood group gene using PCR and direct sequencing methods. We found 16 single nucleotide polymorphisms, two insertion-deletion polymorphisms and two sequence polymorphisms. One of the insertion-deletion polymorphisms was found at nts from -9605 to -9204, and the alleles of that locus were named ABORR*L (non-deletion) and ABORR*S (52-base-deletion).

Mycobacterium bovis BCG cell wall-specific differentially expressed genes identified by differential display and cDNA subtraction in human macrophages.

We have analyzed the gene expression profile of monocytes in response to a highly purified cell wall fraction of Mycobacterium bovis BCG, a clinically approved adjuvant known as BCG cell wall skeleton (BCG-CWS). It is composed of mycolic acid, arabinogalactan, and peptidoglycan and confers Toll-like receptor 2 (TLR2)- and TLR4-dependent signaling that induces monocytes to differentiate into antigen-presenting cells (APCs). Here we report differential gene expression analysis with BCG-CWS-stimulated versus nonstimulated monocytes.

A-elute alleles of the ABO blood group system in Japanese.

The ABO blood group system is important in forensic genetics, as well as transfusion medicine. Since the elucidation of the molecular basis of ABO gene regulation, nucleotides of variant alleles or suballeles have been analyzed by polymerase chain reaction (PCR)-based methods and sequencing. Ael (A-elute) is one of the subgroups of A in the ABO system.