PURPOSE: Hyper IgM syndrome(HIGM) is characterized by severe recurrent bacterial infections with decreased serum levels of IgG, IgA, and IgE but elevated IgM levels. Recently, it has been classified into three groups; HIGM1, HIGM2 and a rare form of HIGM. HIGM1 is a X-linked form of HIGM and has now been identified as a T-cell deficiency in which mutations occur in the gene that encodes the CD40 ligand molecule. HIGM2 is an autosomal recessive form of HIGM. Molecular studies have shown that the mutation of HIGM2 is in the gene that encodes activation-induced cytidine deaminase(AID). Recently, another rare form of X-linked HIGM syndrome associated with hypohydrotic ectodermal dysplasia has been identified. We encountered a patient with a varient form of HIGM2. To clarify the cause of this form of HIGM, we evaluated the peripheral B cells of this patient. METHODS: The lymphocytes of the patient were prepared from peripheral blood. B cells were immortalized with the infection of EBV. Cell cycle analysis was done with the immortalized B cells of the patient. Peripheral mononuclear cells were stained with monoclonal anti-CD40L antibody. Total RNA was extracted from the peripheral mononuclear cells. After RT-PCR, direct sequencing for CD40L gene and HuAID gene were done. Immunostainings of a lymph node for CD3, CD23, CD40, Fas-L, bcl-2, BAX were done. RESULTS: The peripheral B cells of this patient showed normal expression of CD40L molecule and normal sequencing of CD40L gene, and also normal sequencing of AID gene. Interestingly, the peripheral B cells of this patient showed a decreased population of G2/mitosis phase in cell cycles which recovered to normal with the stimulation of IL-4. CONCLUSION: We suspect that the cause of increased serum IgM in this patient may be from a decrease of G2/mitosis phase of the peripheral B cells, which may be from the decreased production or secretion of IL-4. Therefore, this may be a new form of HIGM.
B-Lymphocytes* ; Bacterial Infections ; CD40 Ligand ; Cell Cycle ; Cytidine ; Ectodermal Dysplasia ; Herpesvirus 4, Human ; Humans ; Hyper-IgM Immunodeficiency Syndrome* ; Hyper-IgM Immunodeficiency Syndrome, Type 1 ; Immunoglobulin A ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulin M ; Interleukin-4 ; Lymph Nodes* ; Lymphocytes ; RNA ; T-Lymphocytes

The indirect fluorescent antibody(IFA) test was used to detect serum IgG and IgM antibodies to Trichomonas vaginalis in 31 vaginal trichomoniasis, 7 candidiasis and in 20 non-infected healthy wonem with antigen prepared from axenic culture of Trichomonas vaginalis isolated from vulvovaginitis patient. The results were as follows: In 31 vaginal trichomoniasis the positive reactions of IgG antibody were 27 in the 1/8 dilution or higher and 4 in the 1/4 dilution whereas in healthy women the reaction showed signigicantly low as in the 1/4 dilution of below. The sensitivity and specificity of IFA test for IgG antibody to trichomonad antigen in this study were 87.1% and 100%, respectively. No significant difference of IgM antibody levels between vaginal trichomoniasis and healthy women was observed. No relation between the levels of IgG and IgM antibodies to trichomonad antigen by IFA test was observed. No relation between the time lapse and the level of serum IgG antibodies in IFA test of vaginal trichomoniasis was regarded. In conclusion the present study suggests that IFA test in trichomoniasis could be a useful tool for detection of anti-trichomonad IgG antibodies and applicable as an immundiagnostic method.
parasitology-protozoa ; Trichomonas vaginalis ; trichomoniasis ; diagnosis ; IgM ; IgG ; immunology

Background: IgM antibody capture ELISA (MAC-ELISA) technique has been widely applied for Japanese Encephalitis Virus (JEV) diagnosis. So far rare internationally commercial kits are available. Thus, the international evaluation of the kit is required as per the recommendation of the WHO. Objectives: To evaluate the quality of the IgM antibody capture ELISA diagnostic kit for JEV produced by the Vietnam National Institute of Hygiene and Epidemiology (NIHE). Subjects and method: In this study, NIID kit was used as control to check the kit from NIHE. Both NIHE and NIID kits were used to detect JEV IgM among 38 serum and 6 CFS samples, which belongs to 5 sample groups (JE patients group, dengue patients group, other viral encephalitis patients group, Tick Born Encephalitis (TBE) patient group and healthy JE vaccinated donors group). Results: The detection of JEV IgM by NIHE kit was concurrent with the NIID kit. There is no positive with the JE in the groups of Dengue patients, TBE, other virus encephalitis patients and JE vaccinated donors. Conclusion: MAC-ELISA kit of NIHE can be used for different diagnosis of JEV and Dengue virus (both viruses are in Flavivirus genus), as well as other viruses caused by encephalitis.
IgM antibody ; ELISA diagnostic kit ; Japanese encephalitis virus

A 2-year-old boy was admitted into the hospital because of cough and fever. Lymph node tuberculosis was noted when he was 2 months old and he was subsequently hospitalized several times because of cough and fever. After hospitalization the laboratory examination showed an increased eosinophia level in blood. The immune function tests shows decreased levels of IgG, IgA, and IgM. The patient had no response to anti-tuberculosis, anti-bacterial, and anti-fungal treatment, resulting in recurrent fever and progressive enlargement of the liver and spleen. Jam-like stools were noted 35 days after admission. B ultrasonography showed suspected intussusception. Laparotomy, reduction of intussusception and ileocecum angioplasty, biopsies of intestinal wall nodules and lymphoglandulae mesentericae, and hepatic biopsy were then performed under general anesthesia. The patient eventually died because of postoperative severe liver damage, disseminated intravascular coagulation and electrolyte disorder. Both the blood culture and hepatic biopsy tests showed Penicillium marneffei infecton. Immunodeficiency gene test was performed on the patient, his bother and their parents. T→G base substitution mutation (IVS1-3 T→G) in the CD40L gene was found in the patient. X-linked hyper-IgM syndrome was thus diagnosed in the patient. His mother was a carrier of the mutated CD40L gene, but his father was normal in the gene test. Hemizygous mutation in the CD40L gene was found in both the patient and his bother.
CD40 Ligand ; genetics ; Child, Preschool ; Eosinophilia ; etiology ; Fever ; etiology ; Hepatomegaly ; etiology ; Humans ; Hyper-IgM Immunodeficiency Syndrome ; diagnosis ; genetics ; Male ; Mutation ; Recurrence ; Splenomegaly ; etiology

Congenital immunodeficiency is one or combined immune defect in immunoglobulin, leukocyte, and complement. These patients have increased susceptibility to respiratory infection. Hence, their infection must be taken care of, tried to gene therapy and stem cell transplantation. We present here a case of hyper-IgM syndrome in an 11-year-old male patient who complained of abdominal distension and abdominal pain. Multiple abdominal masses were detected by abdominal computed tomography (CT) and he was diagnosed with neuroendocrine carcinoma by mass biopsy. There was no evidence of metastasis of cancer cells to the bone marrow, but a dysgranulopoietic feature was noted and he was diagnosed with childhood myelodysplastic syndrome. This is the first report that neuroendocrine carcinoma is associated with childhood myelodysplastic syndrome in hyper-IgM syndrome.
Abdominal Pain ; Biopsy ; Bone Marrow ; Carcinoma, Neuroendocrine ; Child ; Complement System Proteins ; Genetic Therapy ; Humans ; Hyper-IgM Immunodeficiency Syndrome ; Immunoglobulins ; Leukocytes ; Male ; Myelodysplastic Syndromes ; Neoplasm Metastasis ; Stem Cell Transplantation

OBJECTIVE: To detect variant of the CD40L gene and infection of Jamestown Canyon virus (JCV) in a 7-year-and-9-month-old boy with co-commitment progressive multifocal leukoencephalopathy (PML) and X-linked hyper IgM syndrome (XHIGM). METHODS: Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA. The 5 exons and exon/intronic boundaries of the CD40L gene were subjected to PCR amplification and sequencing. Suspected variants were analyzed by using bioinformatic software. The JCV gene was amplified from genomic DNA by nested PCR and sequenced. RESULTS: The child was found to harbor a hemizygous c.506 A>C (p.Y169S) missense variant in exon 5 of the CD40L gene. The variant may affect the TNFH domain of the CD40L protein and result in structural instability and loss of hydrophobic interaction between CD40L and CD40. As predicted by PolyPhen2 and SIFT software, the variant was probably damaging (score = 1.00) and deleterious (score= -8.868). His mother was found to be a heterozygous carrier, while the same variant was not found in his father. Gel electrophoresis of the nested PCR product revealed presence of target JCV band, which was confirmed to be 99% identical with the JCV gene by sequencing. CONCLUSION The patient was diagnosed with co-commitment XHIGM and PML based on the testing of the CD40L gene and JCV infection.
Adult ; CD40 Ligand/genetics* ; Child ; Exons/genetics* ; Female ; Humans ; Hyper-IgM Immunodeficiency Syndrome, Type 1/genetics* ; Leukoencephalopathy, Progressive Multifocal/genetics* ; Male ; Mutation, Missense ; Polymerase Chain Reaction

OBJECTIVES: To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM). METHODS: A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT. RESULTS: After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT (P=0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT (P<0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate (P=0.02) and DFS rate (P=0.04). CONCLUSIONS Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.
Child ; Epstein-Barr Virus Infections ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation/methods* ; Herpesvirus 4, Human ; Humans ; Hyper-IgM Immunodeficiency Syndrome ; Retrospective Studies

BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL.METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio.RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories.CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.
Amyloid ; Angiotensinogen ; Atherosclerosis ; Cardiovascular Diseases ; Cholesterol ; Complement System Proteins ; Immunoglobulin mu-Chains ; Lipoproteins ; Nitric Oxide ; Plasma ; Proteomics ; Serine Proteases ; Thyroxine-Binding Globulin ; Vascular Cell Adhesion Molecule-1 ; Vitronectin

OBJECTIVEMutation in the heavy chain micro (microHC) gene causes a rare type of autosomal recessive agammaglobulinemia. Here we report the molecular and clinical characterization of a compound heterozygous mutation in the microHC gene in a patient with autosomal recessive agammaglobulinemia firstly from China.

METHODA one-year and ten-month-old male patient and his parents were enrolled in this study. No mutation was found in BTK gene. The microHC gene of the patient and his parents were amplified by polymerase chain reaction (PCR) from genomic DNA. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the microHC transcripts. Sequencing was performed directly on the PCR products bidirectionally.

RESULTSSince 8 months of age, the patient had had recurrent fever and persistent cough. He suffered an acute right hemiplegia at 11 months of age and swelling and pain of left hip joint and right knee joint at one year and eight months of age. Cerebrospinal fluid routine examination showed that total cell count was 18 x 10(6)/L [normal range (0 - 15) x 10(6)/L], leukocyte count 7 x 10(6)/L [(0 - 15) x 10(6)/L] and biochemical examination showed protein 0.14 g/L (0.15 - 0.45 g/L), glucose 4.68 mmol/L (2.44 - 4.44 mmol/L) and chloride 116.3 mmol/L (120 - 132 mmol/L). Mycobacterium bovis was identified negative by cerebrospinal fluid smear examination. No obvious abnormity was detected on skull CT examination. Hydrothorax examination showed that total cell count was 848 x 10(6)/L, leukocyte count 785 x 10(6)/L and protein 30.8 g/L (< 30 g/L). Poliovirus isolation from stool sample of the patient was negative. The serum immunoglobulin (Ig) profile was IgG 181 mg/L (normal range, 5.09 - 10.09 g/L); IgM 28.8 mg/dl (400 - 1260 mg/dl) and IgA 22 mg/dl (310 - 670 mg/dl), IgE 4.6 U/ml (normal range < 150 U/ml). There were no B-cells but normal percentage of T-cells (67%) and NK cells (32%) were present in the peripheral blood. The patient had a compound heterozygous mutation in the microHC gene:on one allele, there was an alternative splice site mutation in exon 4 (1956 G > A), for which the patient's father was a carrier. Whereas on the other allele, an insert mutation between 170 and 175 in exon 1 with a premature stop codon (170 - 175 insert C, L11fs60X) was identified, for which the patient's mother was a carrier. The insert mutation in exon 1 of microHC gene was firstly reported. To detect the effect of the splice site mutation in exon 4, microHC cDNA of the patient was amplified by semi-nested PCR. The PCR products were purified and sequenced directly. A 136 bp of intron 4 was found in the transcripts and only the secreted isoform with a missense substitution is present in the patient, while synthesis of the membrane isoform is completely abolished.

CONCLUSIONThis is the first case with autosomal recessive agammaglobulinemia with compound heterozygous mutation in the microHC gene reported from China. A novel mutation in exon 1 was found.

Agammaglobulinemia ; congenital ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA ; genetics ; DNA, Complementary ; genetics ; Exons ; Heterozygote ; Humans ; Immunoglobulin mu-Chains ; genetics ; Infant ; Male ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction

No abstract available.
Immunoglobulin M*