Parasitic infection with Trichuris trichiura influences plasma levels of soluble HLA class I

High levels of sHLA-I(soluble HLA class 1) have been correlated with rejection episodes in solid organ transport recipients and with graft versus host disease in bone marrow recipients. Studies of human infection with parasitic worms of the gut have suggested that certain individuals may be genetically predisposed to intense infection. In this study, the influence of parasitic helminth infection on levels of sHLA-I in plasma was investigated in 155 HLA typed individuals from St. Lucia exposed to the gut parasite Trichuris trichiura. The results confirmed previous findings showing increased levels of sHLA-I in HLA-A9, and in this case HLA-A23 postive individuals. However, HLA-A9 positive individuals with high worm burden had significantly lower levels of sHLA-I in their plasma compared with HLA-A9 positive subjects with low worm burden. These results suggest that the intensity of T. trichiuria infection infection influences the ability of HLA-A9 positive subjects to maintain high levels of sHLA-I. (AU)

Little evidence of HLA-G mRNA polymorphism in Caucasian or Afor-Caribbean populations

HLA-G is a nonclassical class I MHC molecule of unknown function expressed on human trophoblast. The level of polymorphism at the HLA-G locus is of considerable importance, since the paternally inherited gene product is exposed to the maternal immune system during pregnancy. However, previous studies of HLA-G polymorphism using genomic DNA samples have produced conflicting results. Our aim was to investigate polymorphism in trophoblast HLA-G mRNA from pregnancies in ten Caucasian and twelve Afro-Caribbean women by RT-PCR. A similar PCR protocol was also applied to umbilical cord blood genomic DNA from two Caucasian and two Afro-Caribbean neonates. Caucasian cDNA yielded only two different sequences: G*01011, and one containing a previously reported synonymous substitution. Afro-Caribbean samples yielded these sequences as well as one previously reported conservative (leucine-to-isoleucine) substitution. PCR amplification from genomic DNA samples from both populations using previously published primer pairs generated sequences containing multiple substitutions, many of which were nonsynonymous. More than two sequences were produced from genomic DNA from each individual. In contrast, amplification from the same genomic DNA using new primers compleentary to exons of the HLA-G gene yielded the same few sequences generated from cDNA. These results suggest that polymorphism at the HLA-G locus is extremely limited in Caucasian and Afro-Caribbean populations. This suggests that spurious polymorphism has been reported in African Americans due to the use of intron-complementary PCR primers on genomic DNA samples. The monomorphic nature of HLA-G may allow trophoblast to carry out the immunological functions of class I-bearing tissues without compromising successful pregnancy.(Au)

Systemic lupus erythematosus, rheumatoid arthritis and HLA phenotypes in Jamaicans

The HLA phenotypes were investigated in 30 Jamaican patients with systemic lupus erythematosus (SLE), 30 with rheumatoid arthritis (RA) an d forty healthy controls. HLA phenotypes were determined by the microcytotoxicity technique, using commercially prepared typing trays. In this study, the HLA phenotypic associations with SLE (HLA-B14, RR 4.3: HLA-A28, RR 4.3) were not statiscally significant. However, a statistically significant lack of HLA-A9 (p<0.01;CP<0.1) was observed in SLE patients compared to healthy controls. In RA patients, a statistically significant associations was noted with HLA-A2 (RR5.1; CP<0.01). No HLA class 11 associations were noted with SLE. Class 11 associations with RA did not achieve statistical significance but included those previously established in other populations. The preliminary data obtained from this study indicate differences in the patterns of HLA phenotypes in Jamaican patients with SLE and RA compared to those observed in such patients elsewhere. Further studies involving larger groups of patients and typing at the serological, cellular and molecular levels are clearly warranted (AU)

Distribution of HLA and haplotypes of Colombian and Jamaican black populations

To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three-locus haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaica were originated from African blacks and admixed variably with Caucasians and South Americans Indians to make genetic subpopulations in Colombia and Jamaica. (AU)

HLA studies in a family with hereditary nephritis - abstract

In 1968, a four-year-old female (the index case) presented with post-streptococcal acute glomerulonephritis (PSAGN). A family visit was made and several members were found to have proteinuria and haematuria without evidence of PSAGN. This family was followed for over 20 years during which time six male members developed chronic renal disease (CRD). Three have since died and two of the three alive are now on dialysis. Mild proteinuria and/or haematuria has been found in other family members of the F and F 2 generations comprising 47 individuals. These observations led to the hypothesis that certain HLA antigens and/or haplotypes are associated with development of CRD in this family. HLA-A,B,C and DR typing were done on 25 available family members, 22 being absent for various reasons including migration. The studies revealed a homozygous condition for HLA-DR2 in the mother, resulting in the inheritance of DR2 in all siblings of the mother. Four of the five female offspring have been studied but only two have had proteinuria and haematuria. However, all male members of the f1 generation had copious proteinuria and three of the five studied had severe haematuria. More importantly, several members of the F 2 generation have already developed mild proteinuria and one female has severe haematuria though they are all clinically normal. Since it has been suggested that males of affected females tend to develop CRD, male offspring of the F 2 generation will be carefully monitored in future (AU)

Myasthenia gravis and HLA phenotypes in Jamaicans

We determined HLA-antigen frequencies and corresponding relative risks (RR) in 30 Jamaicans with myasthenia gravis (MG) and 40 normal controls.. using a microcytotoxicity assay and commercially prepared typing trays, we found that the strongest HLA associations with MG in Jamaicans were with HLA-A2 (RR = 6.15), HLA-B8 (RR = 3.4), HLA-B13 (RR=7.6), and DQw4 (RR = 3.8). After correction of the P value for the number of antigens tested, only HLA-A2 was stastistically significantly increased in MG patients. There was a statistically significant negative association between Mg and HLA-DR2, as well as as HLA-A9 and -B5. No correlation was observed between HLA phenotype, thymic disease, clinical grades, or disease course. HLA-A2 and sex were independent risk factors for MG, female patients having a higher risk (RR = 5.8). Further studies using larger patient and control groups, locally derived typing sera, and DNA probe analysis are indicated. (AU)

Frequency of HLA A, B and C antigens in haematological malignancies in Jamaica - abstract

Our first paper on HLA showed the distribution of the HLA antigens in the Jamaican population and compared the gene frequencies obtained by other workers studying other racial groups. In this paper we use our first study as the basis for examination of disease associations. A flotation density method was used to separate lymphocytes from the peripheral blood of patients attending the University Hospital Haematology Clinic and HLA typing performed using the micro lymphocytotoxicity technique. One hundred and twenty-three patients with varying haematological malignancies were studied. Non-Hodgkin's lymphoma - 70, multiple myeloma - 11, hodgkin's disease - 8, acute myeloid leukaemia - 3, Chronic myeloid leukaemia - 3, acute lymphoblastic leukaemia - 11, chronic lymphocytic leukaemia - 17. We were unable to show any significant association between any of the HLA antigens identified and the haematological malignancies studied. The possible link with the AýB12 haplotype that some workers have reported was not supported by our findings. The most prevalent antigens in this group were mostly the antigens found to be the most prevalent in the 'normal' study group. Of significance, however, were the high frequency of the Cw7 antigen in the myeloma patients and the fact that the Cw4 antigen was almost absent from this group although this antigen shows highest frequency for any antigen for any of the groups tested and is also very high frequency in the normal population. The small number (11) of myeloma patients in this study made it difficult to state a clear association. We look forward to a study of larger numbers of myeloma patients in order to investigate what appears to be an association (AU)

HLA association in Jamaica patients with myasthenia gravis - abstract

Thirty-two (32) Jamaicans with ocular or generalised myasthenia gravis (MG) as well as 40 normal controls were investigated for HLA-A, -B, -C and -DR antigens. HLA antigens contribution to relative risk (RR) in MG patients included HLA -A2 (RR = 615), HLA -B8 (RR = 3.4), HLA-13 (RR=7.76), HLA -DRw8 (RR = 1.34), HLAw12(RR = 1.89), HLA-DQw2(RR = 2.0), HLA -DQw3 (RR = 2.1) and HLA -DRw4 (RR = 3.8). The strongest associations were, therefore, HLA, -A2, -B8, -B13, DQw4. After correction of the 'P value" for the number of antigens tested, only HLA-A2, was significantly increased in MG patients compared to normal Jamaicans. The -DR3 haplo-type which is usually associated with auto-immune diseases was absent in Jamaican MG patients and present in only 5 percent controls. There was a paucity of auto-immune conditions associated with MG in this study. Several of the HLA associations found in Jamaican MG patients correspond to those found in other ethnic groups. However, HLA antigens associated with MG in Jamaican patients were more in agreement with those found in Japanese patients. The HLA types found in Jamaican MG patients did not correlate with thymic pathology, serum concentrations of acetylcholine receptor antibodies, clinical grades or disease course (AU)

Glanzmann's thrombasthenia and pregnancy

Glanzmann's thrombasthenia is a rare congenital disorder of platelet function manifesting as defective primary haemostasis. Bleeding episodes often require platelet transfusions, and allo-immunization to donor platelets may occur. The problems of ensuring adequate haemostatic potential for delivery of an allo-immunized pregnant female with Glanzmann's thrombasthenia are presented (AU)

Genealogical and genetical African admixture estimations, blood pressure and hypertension in a Caribbean community

This study examines the relationships between blood pressure, prevalence of hypertension, and the degree of black African admixture in the population of the Caribbean Island of La Desirade which is homogenous with respect to the environmental factors and for which the socioeconomical stratification does not match racial origin. The degree of admixture was estimated by using both genealogical information and genetic markers. Blood pressure was repeatedly measured using an automatic sphygmomanometer. After adjustment for age, sex, ponderal index, Na/K urinary ratio, and clinical alcoholism, blood pressure and prevalence of hypertension were found to be significantly higher for the individuals having the largest proportion of genes of black origin. Identical results were obtained when either genetic markers or genealogical information were used as an individual-estimator of admixture. (AU)

Immunophenotypic and HLA studies in childhood acute lymphoblastic leukemia in Trinidad, West Indies

Between October 1983 and May 1986, 17 cases of childhood acute lymphoblastic leukemia (ALL) were admitted to the General Hospital, Port of Spain, Trinidad. Fifteen of those cases were under 10 years of age, seven of whom presented with joint or bone pains. Boys outnumbered girls by almost 5:1 and the ethnic distribution showed a preponderance of patients of East Indian origin. At last follow-up (May 1989), the survival rate of the 15 under-ten-year-old patients was 71 percent. Immunophenotype studies on nine of the 17 patients revealed six carrying T cell markers and three carrying markers suggestive of a pre-B phenotype. HLA tissue typing on ten patients showed an enhanced frequency of the HLA-B40 antigen when compared with controls (p less than 0.05). This antigen was present in six of the patients typed and four carried the HLA-A2 and B40 antigens together, two of whom also carried the CW3 antigen and the other two carried untypable C antigens. Three of the four carrying HLA-A2 and B40 have died. Two of the three pre-B cases also carried the HLA-A2 and B40 antigens. HLA studies on three of the four families showed that HLA-A2 and B40 were on the same chromosome, i.e., a haplotype inherited from the mother in each case. None of the cases carried the HLA-B5 antigen although this antigen had a frequency of 37.8 percent in the control group (p less than 0.05 percent). None of the controls with the HLA-B40 antigen carried the CW3 antigen. Further evidence of a disease association must await typing of the D locus antigens but current evidence would suggest an association between HLA-B40 and childhood ALL in Trinidad. (AU)

Genetic susceptibility to leprosy on a Caribbean Island: linkage analysis with five markers

Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae. (AU)

HLA antigens in diabetics of African descent in Trinidad - abstract

The pattern of HLA distribution was studied in one hundred and fifteen Trinidadian diabetics of African ancestry. Insulin-dependent diabetes (IDDM) patients showed a positive association with HLA - A11 and B5 antigens (p<0.05) with relative risks of 5.9 and 3.2 respectively. In addition, HLA -B8 showed a positive but not statistically significant deviation, while HLA - B12 showed a negative association (relative risk 0.27). There was no association found between HLA -B15 and IDDM. Maturity-onset diabetics (MODM) showed positive association with HLA - B5 (p <0.025 and relative risk 2.93), and a significant negative association with HLA - A2, A3 and A9. In most populations, strong associations may be found between certain HLA antigens and IDDM, the associations" varying depending on the ethnicity of the population. Interestingly, no association has been observed between HLA antigens and MODM in Caucasian populations. However, several workers have observed significant deviations of HLA antigens in indigenous African MODM patients. In addition, the inconsistency of HLA antigen associations with IDDM in persons of African ancestry compared to that in Caucasians has led to the suggestion that diabetes mellitus in native Africans is genetically different from that in Caucasians. Our findings would tend to support this view (AU)

Search for reiter's syndrome after an outbreak of shigella sonnei dysentery

Forty-seven percent of 4,205 individuals living in a Puerto-Rican community developed shigella sonnei dysentery. Questionnaire and, where relevant, clinical evaluation of 1,970 patients and the remaining 2,235 unaffected residents disclosed no cases of reiter's syndrome (RS). Among the possible explanations for failure to observe any cases is the important suggestion that s. sonnei is not arthritogenic (AU)