RNA and protein expression of HLA-A(∗)23:19Q.

The assignment of null alleles is clinically relevant in stem cell transplantation, in particular for donor selection. It is unclear how questionable (Q) alleles, having an unknown expression profile, should be considered in matching criteria. In this study we analyzed the RNA and protein expression profile of a questionable allele encountered in a sample of the Guadeloupe population: GD23Q, HLA-A(∗)23:19Q, 29:02:01. Full-length DNA sequencing of HLA-A(∗)23:19Q revealed a single polymorphism at position 619 (G>A) compared to HLA-A(∗)23:01:01. Serological typing showed only the presence of HLA-A29; HLA-A(∗)23:19Q was not detected on the cell surface. The absence of HLA-A(∗)23:19Q surface expression was shown by flow cytometry using a directly labeled monoclonal antibody and a panel of five indirectly labeled polyclonal antibodies all directed against HLA-A23 (HLA-A9) molecules. Allele specific amplification revealed the absence of intact full-length mRNA, but the presence of two major alternatively spliced mRNAs: sequencing identified that in one variant exon 3 is missing and in the other variant introns 2 and 3 are retained. Based upon the lack of HLA-A(∗)23:19Q surface expression and the presence of aberrant mRNA transcripts only, this study shows that HLA-A(∗)23:19Q is non-expressed.

Allele and haplotype frequencies of HLA-DPA1 and -DPB1 in the population of Guadeloupe.

Genetic polymorphism of human leukocyte antigen (HLA)-DPA1 and -DPB1 loci was studied in 154 unrelated individuals from Guadeloupe, an archipelago of five islands located in the Carribean Sea. Thirty different DPB1 and eight different DPA1 alleles were observed with a heterozygosity index of 0.87 and 0.78, respectively. This high degree of heterozygosity corresponds with those found in African populations. The DPB1* 01:01:01 allele was most frequent (0.260), followed by 02:01:02 (0.143) and 04:01:01 (0.127). The DPA1 alleles 01:03 (0.380), 02:01 (0.302), 02:02 (0.175) and 03:01 (0.123) were identified in >35 individuals each, whereas 01:04, 01:05 and 04:01 were present only once. Haplotype estimations revealed the presence of 39 different haplotypes, with DPB1*01:01:01-DPA1*02:02 and DPB1*02:01:02-DPA1*01:03 as the most frequent (0.143 and 0.140, respectively). A striking difference was observed in DPB1/DPA1 associations between DPB1*04:02 and *105:01, that have identical exon 2 sequences. DPB1*04:02 was exclusively associated with DPA1*01:03, whereas DPB1*105:01 was present with DPA1*03:01, *03:02 or *04:01. This implies that the DP molecules are actually different, and this difference is relevant to consider in studies on the function of HLA-DP molecules in transplantation. Overall, HLA-DPA1 and DPB1 allele frequencies and haplotypes of the population of Guadeloupe were most similar to African populations, with characteristic alleles and haplotypes that bespeaks the admixture with other ethnicities.

Full-length sequence of a novel HLA-B*15:220 allele identified in an individual from Guadeloupe.

The new HLA-B*15:220 allele shows a single-nucleotide substitution in exon 1 at position 47 (C>T) when compared to its closest allele HLA-B*15:03:01, resulting in an amino acid substitution from Ala to Val in the signal peptide at codon -9.

Full-length sequence of a novel null allele HLA-A*23:38N identified in an individual from Guadeloupe.

The new HLA-A*23:38N allele shows a single-base deletion in exon 2, resulting in a frame shift and a premature stop codon.

Optical switching and detection of 640 Gbits/s optical time-division multiplexed data packets transmitted over 50 km of fiber.

We demonstrate 1×4 optical-packet switching with error-free transmission of 640 Gbits/s single-wavelength optical time-division multiplexed data packets including clock distribution and short pulse generation for optical time demultiplexing based on a cavityless pulse source.

Evidence for the chronic in vivo production of human T cell leukemia virus type I Rof and Tof proteins from cytotoxic T lymphocytes directed against viral peptides.

Human T cell leukemia virus type I (HTLV-I) is a persistent virus that causes adult T cell leukemia and tropical spastic paraparesis/HTLV-I-associated myelopathy. Studies on rabbits have shown that viral proteins encoded by the open reading frames pX-I and pX-II are required for the establishment of the persistent infection. To examine the in vivo production of these proteins in humans, we have investigated whether cytotoxic T lymphocytes isolated from HTLV-I-infected individuals recognized pX-I and pX-II peptides. CD8(+) T lymphocytes to pX-I and pX-II peptides were detected in HTLV-I-infected individuals, whatever their clinical status, and even in the absence of any antigenic restimulation. These findings indicate that the HTLV-I pX-I and pX-II proteins are chronically synthesized in vivo, and are targets of the natural immune response to the virus.

Geographical clustering of human T-cell lymphotropic virus type I in Guadeloupe, an endemic Caribbean area.

Between January 1989 and December 1996, 59,426 blood donors from Guadeloupe (French West Indies) were screened for antibodies to human T-cell lymphotropic virus type I (HTLV-I). Of these, 195 were confirmed as being positive for HTLV-I, yielding an overall prevalence of 0.33% [95% confidence interval (CI) 0.28-0.38]. On multiple logistic regression analysis, risk factors for HTLV-I were female gender [odds ratio (OR) 1.8; CI 1.3-2.4], increasing age (30-39 years, OR 2.2, CI 1.4-3.4; 40-49 years, OR 3.1, CI 2.1-4.7; > or =50 years, OR 5.6, CI 3.6-8.6) and positive hepatitis B core antibodies (OR 2.0; CI 1.5-2.8). HTLV-I seropositivity was also significantly associated with current residence in certain areas, highlighting microgeographic clustering: individuals living along the Atlantic Facade of Guadeloupe, which is a traditional sugar cane plantation area where Africans were brought during slave trading, were at increased risk for HTLV-I infection (OR 1.9; CI 1.3-2.7) compared with other areas in Guadeloupe devoted to other activities. Our report of HTLV-I cluster identification in Guadeloupe probably reflects both its low spread and its highly intrafamilial restricted transmission within this endemic Caribbean population.

Prevalence of GB virus type C/hepatitis G virus RNA and of anti-E2 in individuals at high or low risk for blood-borne or sexually transmitted viruses: evidence of sexual and parenteral transmission.

BACKGROUND: The first epidemiologic evidence of GB virus type C (GBV-C)/hepatitis G virus (HGV) infection showed a high prevalence of asymptomatic carriers in blood donors and in populations at risk for blood-borne viruses. However, by using only viral RNA polymerase chain reaction, those studies underestimated the true spread of GBV-C/HGV infection. The combined detection of GBV-C/HGV RNA and of anti-E2 (which reflects recovery from infection) is necessary to define accurately the prevalence of GBV-C/HGV. STUDY DESIGN AND METHODS: The presence of both anti-E2 and GBV-C/HGV RNA was searched for in 1438 serum samples collected from various groups of individuals at low or high risk for blood-borne or sexually transmitted viruses (blood donors, organ donors, unselected pregnant women, immunocompetent or immunodepressed multiply transfused patients, HIV-positive or HIV-negative homosexual men, intravenous drug addicts). RESULTS: The presence of GBV-C/HGV RNA and/or anti-E2 (exposure to GBV-C/HGV) was frequent in populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV appeared also to be sexually transmitted, with transmission from male to female more efficient than vice versa. A particularly elevated level of exposure to GBV-C/HGV was observed in homosexual men. In immunocompetent individuals, the prevalence of anti-E2 was about twice that of GBV-C/HGV RNA, which suggests the frequency of recovery from GBV-C/HGV infection. Most of the GBV-C/HGV RNA-positive individuals had no biochemical evidence of liver damage. CONCLUSIONS: GBV-C/HGV is frequent in populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV is not a hepatitis virus, and it seems appropriate to rename it.

Hepatitis B virus infection on a tropical island: sociodemographic and geographic risk factors in Guadeloupe.

A seroepidemiologic study on a cross-sectional sample of blood donors was carried out in Guadeloupe, a French West Indies island, to estimate the prevalence of hepatitis B virus (HBV) markers, and to investigate the influence of age, socioeconomic, and geographic factors on prior HBV infection. Blood specimens and sociodemographic data were collected in 1989 from 2,339 blood donors residing on the island. A total of 73 (3.1%) of 2,339 were found to be HBV surface antigen carriers, and 518 (22.1%) were positive for antibody to HBV core antigen. Among them, 61 were positive for both markers and consequently 530 persons (22.7%) were considered to have evidence of prior HBV infection. Multivariate logistic regression analyses identified age and low socioprofessional status as being related to HBV infection, as in many endemic areas. In addition, some major geographic risk factors were highlighted, reflecting a strongly hyperendemic situation in specific areas and the potential influence of horizontal transmission or unknown environmental factors on these particular populations.

An unique seroepidemiological situation for hepatitis B markers in Guadeloupe: results of a prospective study in blood donors - abstract

Screening for HBsAG, anti-HBc, anti-HCV and ALAT levels is now performed on donor blood to prevent post-transfusion hepatitis. A prospective study of 2368 blood donors was performed in Guadeloupe (French West Indies) to determine risk factors associated with serologic abnormalities: 571 blood donations (24 percent) were positive for at least 1 of the 4 markers with 3.2 percent positive for HBsAG, 22 percent for anti-HBc, 0.8 percent for anti-HCV and 1.4 percent for ALAT (<45 IU/L). The anti-HCV prevalence was significantly different according to ALAT levels (P<10). Transfusion histosry and employment status (worker or serviceman) were found to be risk factors, with an odds ratio (OR) of 1.94 for serviceman population. Other unexpected risk factors were: number of years' residency in Guadeloupe (progressively increased risk with increasing number of years); birthplace and residence in the southern part of the island as well as the existence of gastrointestinal discomfort unrelated to viral hepatitis (OR=2.91). The results of this study show a unique epidemiological situation for hepatitis B virus in Guadeloupe necessitating careful selection of blood donors (AU)

Epidemiologic comparison of human T-lymphotropic virus type I-infected blood donors from endemic and nonendemic regions over a 3-year period.

BACKGROUND: Screening for human T-lymphotropic virus type I (HTLV-I) infection became systematic in 1989 in the French West Indies for blood from all donors and in France for blood from natives of endemic areas; in 1990, it was extended to blood from donors with at-risk sex partners and in July 1991 to blood from all donors. STUDY DESIGN AND METHODS: The epidemiologic characteristics of individuals found through the screening of donated blood to be HTLV-I infected were compared for an endemic region (Guadeloupe, French West Indies) and a nonendemic region (Paris area) over a 3-year period (1989 through 1991). RESULTS: In Guadeloupe, 131 HTLV-I-infected individuals were detected in the screening of 28,801 units; in the Paris area, 38 HTLV-I-infected donors were detected in the screening of 109,824 units. All Guadeloupean HTLV-I-infected donors were natives of endemic areas. Among the 38 Parisian HTLV-I-infected donors, 21 were natives of endemic areas, 10 were natives of endemic areas and had received transfusions, 2 were whites who had received transfusions, and 5 were whites who had had heterosexual contact with natives of endemic areas. The percentage of HTLV-I-infected individuals whose blood would have been excluded because of positivity for one or more markers for other viruses did not significantly change over the study period and did not significantly differ between regions (41%). Among the eight Parisian HTLV-I-infected blood donors detected after July 1991, six would not have been detected without the biologic screening. CONCLUSION: The generalization of biologic screening of HTLV-I-infected donated blood in France was useful for the prevention of HTLV-I and HTLV type II infections through transfusion.

Human T-cell lymphotropic virus type I and II DNA amplification in seropositive and seronegative at-risk individuals.

To determine the presence or the absence of human T-lymphotropic virus type I and/or II (HTLV-I/II) DNA in at-risk individuals who were persistently negative for specific serologic assays, polymerase chain reaction with two primer pairs in common and conserved regions of HTLV-I and -II genomes was used. Seronegative individuals at risk for HTLV-I/II infection (15 heterosexual partners of seropositive individuals, 17 breastfed children born to HTLV-I-infected mothers, 47 multiply transfused patients, 22 intravenous drug users) were studied (n = 101); 35 seropositive individuals and 25 seronegative low-risk individuals were used as positive and negative controls, respectively. No positive polymerase chain reaction was observed in the seronegative at-risk individuals or in the negative controls. Positive controls gave positive results with at least one primer pair in all cases except one. A latent HTLV-I/II infection with a persistently negative serologic test for HTLV-I/II seems unlikely.

A unique seroepidemiologic situation for hepatitis B markers in Guadeloupe. Results of a prospective study in blood donors.

Screening for HBsAg, anti-HBc, anti-HCV and ALAT levels is now performed on donated blood to prevent post-transfusion hepatitis. A prospective study of 2,368 blood donors was performed in Guadeloupe (French West Indies) to determine risk factors associated with serologic abnormalities: 571 donations (24%) were positive for at least 1 of the 4 analyzed markers with 3.2% positive for HBsAg, 22% for anti-HBc, 0.8% for anti-HCV and 1.4% with ALAT > or = 45 IU/L. The anti-HCV prevalence was significantly different according to ALAT levels (P < 10(-4)). Transfusion history and work status (worker or serviceman) were found to be risk factors, with an odds ratio of 1.94 for serviceman population. Other unexpected risk factors were: number of years residency in Guadeloupe (progressively increased risk with the number of years), birthplace and residence in southern part of the island as well as the existence of gastrointestinal discomfort unrelated to viral hepatitis (odds ratio = 2.91). The results of this study show a unique epidemiologic situation for hepatitis B virus in Guadeloupe necessitating careful selection of blood donors.

Risk factors associated with hepatitis B or C markers or elevated alanine aminotransferase level among blood donors on a tropical island: the Guadeloupe experience.

Donated blood is currently screened for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis C virus (anti-HCV), and alanine aminotransferase (ALT) levels to prevent posttransfusion hepatitis. A prospective study of 2368 blood donors was carried out in Guadeloupe (French West Indies) with a view to determining the risk factors associated with serologic abnormalities. Blood donors included in the study had to complete a questionnaire. Statistical analysis was performed on the data thus obtained: 571 donations (24%) were positive for at least one of the four analyzed markers. The results were that 3.2 percent were positive for HBsAg, 22 percent for anti-HBc, and 0.8 percent for anti-HCV, and 1.4 percent had ALT > or = 45 IU per L. A good correlation was found between anti-HCV and elevated ALT. Transfusion history and two socioeconomic categories (working class, military personnel) were found to be risk factors. Other risk factors were lifelong residence in Guadeloupe (with risk increasing with the number of years), birthplace and current residence in the southern part of the island, and the existence of gastrointestinal discomfort unrelated to viral hepatitis (odds ratio = 2.98). The results of this study illustrate the difficulty of implementing a preventive policy against posttransfusion hepatitis in a tropical area. The unique epidemiologic situation of Guadeloupe as regards hepatitis B virus has led to more restrictive criteria for the acceptance of blood donors.

Human T lymphotropic virus (HTLV) type I and II DNA amplification in HTLV-I/II-seropositive blood donors of the French West Indies.

To confirm the presence of DNA from human T lymphotropic virus type I (HTLV-I), HTLV-II, or both in individuals found HTLV-I/II-positive through systematic screening of blood donations in Guadeloupe (French West Indies), 42 blood donors repeatedly positive for HTLV-I/II by ELISA were studied by polymerase chain reaction (PCR). Three primer pairs (env, pol, tax) targeted on conserved regions of HTLV-I or -II sequences (or both) and six probes (two generic, two HTLV-I-specific, two HTLV-II-specific) were used in a multiplex PCR. HTLV-I sequences were detected in 31 individuals (74%). All 31 subjects positive by Western blot (WB) harbored HTLV-I sequences. Fifteen individuals (48%) were positive with the three primer pairs used, 10 (32%) with two, and 6 (20%) with one. Subjects indeterminate or negative by WB were all negative by PCR. No HTLV-II sequences were detected with specific probes. The results indicate the absence of HTLV-I and -II infection in individuals with indeterminate WB, the presence of HTLV-I DNA in individuals positive for WB in the French West Indies, and the absence of HTLV-II infection in the cohort.

Quantification of HTLV-1 proviral copy number in peripheral blood of symptomless carriers from the French West Indies.

The development of human T-cell leukemia type 1 (HTLV-1) diseases are related to an increase in the proviral copy number (VCN) in peripheral blood mononuclear cells (PBMCs). Twenty symptomless anti-HTLV-1-positive blood donors, as well as four symptomatic individuals, all from the French West Indies, were studied. The VCN in PBMCs was determined by quantitative PCR. The VCN values for asymptomatic HTLV-1 carriers (range of less than 100 to approximately 9,500/micrograms of DNA) was nearly always less than the values for symptomatic carriers (range of approximately 5,500 to approximately 29,000/micrograms of DNA). Consequently, the proportion of HTLV-1-infected PBMCs in symptomless and in symptomatic individuals ranged from less than 1/1,500 to approximately 1/16 and approximately 1/27 to approximately 1/5, respectively. No correlation could be found between VCN and age or sex, suggesting the importance of factors other than age and sex as influences on the VCN number.

No evidence of HTLV-I infection in French patients with multiple sclerosis using the polymerase chain reaction.

The polymerase chain reaction (PCR), using three primer pairs in the pol, tax, and env regions of the HTLV-I genome, was unable to detect HTLV-I in the blood samples of 54 caucasian subjects with multiple sclerosis who were seronegative for HTLV-I/II. Seventeen HTLV-I/II seropositive (by ELISA and Western blot) subjects used as positive controls were positive with the three primer pairs. The PCR was negative in 47 healthy HTLV-I/II seronegative (by ELISA) subjects at low risk of HTLV-I infection used as negative controls. These results suggest that there is no association between the occurrence of HTLV-I sequences and the development of multiple sclerosis.

[Prevention of post-transfusion hepatitis in Guadeloupe: results after application of new measures for detecting blood donors potentially at risk]. / Prévention des hépatites post-transfusionnelles en Guadeloupe: résultats obtenus après application des nouvelles mesures visant à détecter les donneurs de sang potentiellement à risque.

One of the main concerns of blood transfusion centers is viral hepatitis as a direct result of blood transfusion. Ninety-five percent of these cases are non-A, non-B hepatitis. In order to prevent this disease, blood collections were screened for antibody anti-HBc as well as the level of activity of the alanine aminotransferase in 3,051 blood donors in Guadeloupe. this revealed a particular epidemiological situation, which caused this French country to be rated among moderate endemic zones for hepatitis B virus. As a result of this new screening procedure, 25 percent of the blood collected had to be discarded and was classified with prevalence rates of 21.8 percent HBc antibody, 2.9 percent HBs antigen, and 2.6 percent alanine aminotransferase (45 IU/l). Differences were noted according to sex, age, social-economical level and geographical origin of the blood donors. These data raised many significant questions regarding the vertical transmission of hepatitis B virus, the epidemiological situation of hepatitis B virus in the Guadeloupe population as well as in the rest of the French West-Indies, and also the type of action which must be taken against non-A, non-B hepatitis in a moderate endemic zone for HBV.