Human Leucocyte Differentiation Antigen nomenclature: update on CD nomenclature. Report of IUIS/WHO Subcommittee

The 7th International Workshop on Human Leucocyte Differentiation Antigens (HLDA7) studied a number of newly characterised molecules relevant to human leucocyte differentiation and function. The HLDA organisation, which devised and continues to maintain the CD nomenclature, is responsible, under the auspices of IUIS and WHO, for the nomenclature of all leucocyte differentiation markers. The 7th Workshop redefined a number of (principally carbohydrate) molecules, and assigned CD names to approximately 80 new molecules. This update lists, in tabular form, the redefined and newly assigned names, together with antibodies, which have been confirmed under Workshop conditions as specific for the new and redefined molecules. The major features of the cellular expression patterns are summarised, and a LocusLink accession number provided to enable the reader to access more detailed information through http://www.ncbi.nlm.nih.gov/LocusLink.     

Adjustment in Childhood Brain Tumor Survival: Child, Mother, and Teacher Report

Examined the adjustment of 6- to 18-year-old children and adolescents(n = 38) 2 to 5 years postdiagnosis of brain tumor with respectto standardized measures of anxiety and depression; self-perceptions;and adaptive living skills. Child, mother, and teacher reportdata were used. Maternal adjustment (anxiety and depression,parenting stress) was also assessed. Children and adolescentssurviving brain tumors reported themselves to be generally withinthe normal range. However, maternal ratings of social problemswere higher than normative scores and significantly lower thannorms on social problems, scholastic competence, and communicationskills. Teacher ratings on the Teacher Rating Form were allwithin normal limits. Maternal adjustment measures were withinthe normal range, although the Parent-Child Dysfunctional Interactionsubscale of the Parenting Stress Index was elevated. No differencesin scores were found between children in regular and specialeducation, or between children who had received radiation andthose who did not. This sample of survivors of pediatric braintumors and their mothers had relatively mild problems in adjustment,supporting a competency-based view of the adaptation of pediatricpatients and their families.     

A prospective, randomized, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization

Urinary follicle stimulating hormone (FSH) is being used forthe treatment of human infertility. Recently, FSH manufacturedby means of recombinant DNA technology with a much higher purity(>99%) has become available. A prospective, randomized, assessor-blind,multicentre (n = 18) study was conducted in infertile womenundergoing in-vitro fertilization comparing recombinant FSH(Org 32489, Puregon®) and urinary FSH (Metrodin®). Eligiblesubjects were randomized (recombinant versus urinary FSH = 3:2)and pretreated with buserelin for pituitary suppression. FSHwas given until three or more follicles with a diameter of atleast 17 mm were seen. After oocyte retrieval, fertilizationroutines were applied according to local procedures. No morethan three embryos were replaced. In all, 585 subjects receivedrecombinant FSH and 396 urinary FSH. Significantly more oocyteswere retrieved after recombinant FSH treatment (mean adjustedfor centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancyrates per attempt and transfer in the recombinant FSH groupwere 22.17 and 25.97% respectively, and in the urinary FSH group,18.22 and 22.02% respectively (not significant). Ongoing pregnancyrates including pregnancies resulting from frozen-thawed embryocycles were 25.7% for recombinant and 20.4% for urinary FSH(P = 0.05). Compared to urinary FSH, the total dose of FSH wassignificantly lower with recombinant FSH (2138 versus 2385 IU,P < 0.0001) in a significantly shorter treatment period (10.7versus 11.3 days, P < 0.0001). No clinically relevant differencesbetween recombinant and urinary FSH were seen with respect tosafety variables. It is concluded that recombinant FSH (Puregon)is more effective than urinary FSH in inducing multifolliculardevelopment and achieving an ongoing pregnancy.     

Interleukin 17 modulates the immune response to vaccinia virus infection

Interleukin 17 (IL-17) is a newly identified cytokine that has a homolog in herpesvirus saimiri. We inserted murine IL-17 into vaccinia virus to study the role of IL-17 in viral infection. Vaccinia virus expressing IL-17 (vv-IL17) and its parental control virus (vv-pRB) grew to similar titers in vitro; however, vv-IL17 was more virulent in mice with a threefold lower LD(50) than for vv-pRB, and mean time to death of 2.8 days versus 4.5 days. Mice infected with vv-IL17 had higher titers of virus in the ovaries (P < 0.02) and showed a decrease in NK cell cytotoxicity (P < 0.02) on day 3 after infection. No significant difference was found in CTL activity. In addition, a significant decrease in IgG2a (P < 0.01) and increases in IgG1, IgG3, and IgA (P < 0.03) vaccinia virus-specific antibody titers were observed in mice infected with vv-IL17 versus vv-pRB, suggesting a Th-2-like response to infection. These data indicate that IL-17 modulates the immune response during virus infection.     

Association of haplotypes in the beta-chemokine locus with multiple sclerosis

Linkage studies in multiple sclerosis (MS) identified several susceptibility loci. One of these regions includes chromosome 17q11 where a meta-analysis of data from three genome scans suggested linkage. This region encodes a cluster of genes for beta-chemokines or CC chemokine ligands (CCLs), which may be involved in the development of MS lesions. Here we aimed to test if CCL alleles and haplotypes are associated with MS. Using methods of linkage and association, we observed deviations from the expected 50% transmission of haplotypes from unaffected parents to their affected children at CCL2, CCL11-CCL8-CCL13 and CCL3 within the investigated 1.85 MB chromosomal segment. Analyses of the linkage disequilibrium map support that variants with possible relevance to MS can be located within these subregions. Identification of MS associated CCL variants may have direct clinical significance, as it can lead to the design of small competitive antagonists of these molecules with beneficial effects in the treatment of patients with early and active disease.     

Early steps of a thymic tumor in SV40 transgenic mice: hyperplasia of medullary epithelial cells and increased mature thymocyte numbers disturb thymic export

Bone marrow progenitors migrate to the thymus, where they proliferate and differentiate into immunologically competent T cells. In this report we show that mice transgenic for SV40 T and t antigens under the control of the L-pyruvate kinase promoter develop, in a first step, thymic hyperplasia of both thymocytes and epithelial cells. Morphological studies (histology, immunohistolabeling and electron microscopy) revealed modifications of the thymic microenvironment and gradual expansion of medullary epithelial cells in 1 month-old mice, taking over the cortical region. Then, a thymic carcinoma develops. Two-color labeling of frozen sections identified the transgene in medullary epithelial cells. Flow cytometry analysis demonstrated a marked increase in mature CD4+ and CD8+ thymocytes in adult mice (39 +/- 10 x 10(6) in transgenic mice and 12 +/- 5 x 10(6) in age-matched controls). Furthermore, thymocyte export was disturbed.     

IgG anti-tetanus toxoid antibody synthesis by human bone marrow. I. Two distinct populations of marrow B cells and functional differences between marrow and peripheral blood B cells

This investigation uses a system for inducing and detecting anti-tetanus toxoid antibody (anti-TT) synthesis to study specific antibody (Ab) synthesis by bone marrow mononuclear cells (MC). We measured the amounts of anti-TT secreted and the number of B cells secreting antibody (Ab). The ELISA plaque detects single B cells secreting specific Ab. The results show that (1) spontaneous anti-TT secretion by MC is higher than spontaneous anti-TT secretion by peripheral blood lymphocytes (PBL) using an ELISA plaque (P<0.01); (2) spontaneous anti-TT production by MC correlated with the serum anti-TT titers as measured by an ELISA (r=0.75,P=0.005); (3) two types of marrow B cells were identified—one that spontaneously secretes anti-TT and another that produces anti-TT after TT-stimulation; (4) the frequency of anti-TT-secreting B cells is higher in MC than in PBL; (5) the amount of Ab secreted per marrow B cell is not different from that secreted by a peripheral B cell; and (6) marrow B cells could be induced to produce anti-TTin vitro up to 10 months without added cytokines. These results show that bone marrow is a major repository for differentiated B cells that spontaneously produce Abs to maintain circulating Abs titers and for memory B cells that can be induced to produce specific Ab.     

Clinical Features of Fatal Familial Insomnia: Phenotypic Variability in Relation to a Polymorphism at Codon 129 of the Prion Protein Gene

Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1+ 1.1 months) or a prolonged (30.8 + 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mai seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene.     

Protection from insulin-dependent diabetes mellitus is linked to a peptide transporter gene

HLA class II association with insulin-dependent diabetes mellitus (IDDM) is well established but is still difficult to map to a particular locus. Polymorphism of the genes coding for transporter associated with antigen processing (TAP1 and TAP2), and located in the HLA class II region, was studied in 167 IDDM patients (116 adult-onset and 51 childhood-onset patients) and 98 normal controls using oligotyping after genomic amplification. A dominant protective effect was observed for theTAP2*0201 allele [relative risk (RR)=0.3, corrected probability (pc) < 0.001]. Conversely, susceptibility to IDDM was associated with apparent homozygosity for the TAP2*0101 allele (RR=3.4, pc < 0.001). Protection was independent from but additive to the protection conferred by the DRB1*02 DQB1*0602 haplotype (RR=0.06, pc<0.05), and antagonistic to the DRB1*03 DQB1*0201 and DRB1*04 DQB 1*0302 haplotypes predisposing effect (RR=1.1, not significant), arguing in favor of an absence of linkage disequilibrium between TAP2 and HLA class II genes. This was assessed by x² analysis. TAP1 allelic distribution was not different among diabetics and controls. A significant association was observed between the presence of TAP2*0101 and that of islet cell antibodies (p < 0.05). These data suggest that the TAP2 gene, which encodes protein required for delivery of antigen peptides to class I molecules in the endoplasmic reticulum, could modulate the autoimmune response leading to β cell destruction. From a practical point of view, they make the combined screening of HLA class II and TAP2 loci a highly valuable tool in IDDM prediction.