Interferon-alpha 2b modulation of doxorubicin sensitivity in a multidrug resistant cell line.

We evaluated the effect of interferon-alpha2b as a chemosensitiser on HCT-15 cell line in treatment with doxorubicin. Chemosensitivity was determined by [3H]-thymidine incorporation and tetrazolium assays. The levels of expression of P-glycoprotein, Bcl-2 oncoprotein and HLA-ABC complex, and cell cycle/apoptosis analysis were determined by flow cytometry. Dox 50 ng/ml - IFN alpha 2b 500 IU/ml treatment inhibited cell proliferation (47.2 +/- 1.4%, p < 0.0001; MTT assay: 40.6 +/- 1.2%, p < 0.0001) and augmented the expression of P-170, Bcl-2 and HLA-ABC, while it didn't exert apoptosis, producing a slight G2/M arrest. A concentration of IFN-alpha2b, that by itself is not cytotoxic, can potentiate the efficacy of the anticancer drug. This effect is not due to a down-modulation of P-170. The absence of apoptosis and augmented levels of Bcl-2 expression suggests that this could be one of the mechanisms of drug resistance exerted by these cells.

Both psoriasis and benign migratory glossitis are associated with HLA-Cw6.

This study was undertaken to investigate human leucocyte antigen (HLA) associations with benign migratory glossitis and psoriasis in Brazilian patients and particularly to determine whether benign migratory glossitis is also associated with HLA-Cw6, the classical association observed in psoriasis. The results showed a highly significant association of Cw6 with both psoriasis and benign migratory glossitis, with this antigen being present in 59.1% of the patients with psoriasis, in 43.8% of the patients with benign migratory glossitis, and in only 12.6% of the controls. Other significant positive associations, although at a lower significance level, were with B13, both in psoriasis and in benign migratory glossitis, and with B17, only in psoriasis. To our knowledge, this is the first report on the association of Cw6 with benign migratory glossitis. We believe that this finding reinforces the concept of a pathogenetic relationship between benign migratory glossitis and psoriasis.

Análise de associação entre cardiopatia chagásica crônica e antígenos HLA de classe I (HLA-A, -B e -C) e de classe II (HLA-DR e -DQ) / Analysis of association between chronic Chagas Cardiomyopathy and antigens HLA of class I (HLA It, - B and - C) and of class II (HLA-DR and - DQ)

Considerando que o sistema HLA contem genes que controlam a resposta imune, bem como genes de susceptibilidade genética a diversas doenças, temos como objetivo a realização de um estudo de associação entre os antígenos HLA e a doença de CHAGAS, forma cardíaca. Foram analisadas as freqüências dos antigenos HLA-A, -B, -C, -DR E -DQ em 47 pacientes com cardiopatia chagásica crônica e 95 indivíduos controles. Essas amostras iniciais são constituídas por caucasóides e negroides. As analises estatísticas mostram um aumento estatisticamente significante da freqüência de HLA-DR2 nos pacientes, quando comparados com os controles. a significativo ns freqüências de dr-2, cujas freqüências nos pacientes e controles são de 48,3por cento e 12,3por cento, respectivamente (pc=0,0058). Os resultados sugerem uma associação positiva do antígeno DR-2 com cardiopatia chagásica crônica. Embora os resultados indiquem uma possível associação com DR-2 também em negroides, os nossos dados não são conclusivos para esse grupo racial, devido ao pequeno tamanho da amostra analisada

Lack of association between paracoccidioidomycosis and HLA histocompatibility antigens

Foi realizado um estudo de associaçäo HLA e doença, onde 40 pacientes com diagnóstico clínico e laboratorial de Paracoccidioidomicose (PCM) e, 80 indivíduos brancos, clinicamente saudáveis, usados como controles, foram tipados para os antígenos HLA-A, -B, -Cw, -DR e - DQ. Os resultados obtidos mostraram uma associaçäo positiva dos antígenos HLA-A1 (P = 0.050), -A3 (P = 0.014), -B8 (P = 0.014), -Cw7 (P = 0.020), - DQw2 (P = 0.014) e DQw3 (P = 0.019) nos pacientes e uma associaçäo negativa dos antígenos HLA-Cw3 (P = 0.032), -DR1 (P = 0.019) e -DQw1 (P = 0.003) no mesmo grupo, comparados aos controles e, sem correçäo pelo número de antígenos testados (50). Os resultados sugerem uma fraca associaçäo destes antígenos HLA com a doença, uma vez que outros fatores podem também estar influenciando na susceptibilidade genética à PCM. Se corrigido o valor de P, segundo Svejgaard e Ryder (HLA and disease, J, Dausset and A. Svejgaard, eds., 1977), nenhuma associaçäo é demonstrada neste estudo

[HLA A, B, C and DR antigens in a urban population from Santiago of Chile]. / Antígenos HLA-A, B, C y DR en una población urbana de Santiago de Chile.

HLA antigens vary in different ethnical groups and in Chile there are no reports on the frequency of these antigens in a normal representative population. The few existing studies are of indigenous populations and control groups, without including HLA-DR antigens. Therefore, the aim of this study was to study the frequency of HLA A, B and C antigens in 349 individuals and HLA-DR in 257, using the microlymphocytotoxicity method, and compared the results with those on normal caucasian populations (Europe and USA). Significant differences were found for 7 antigens of group A, 10 of group B, 4 of group C and 6 of group DR. The observed difference allow us to conclude that the population from Santiago has a distinct HLA antigen distribution. This fact must be bore in mind future studies in genetics, paternity or autoimmune diseases.

[HLA antigens in Chagas cardiomyopathy: new evidence based on a case-control study]. / Antígenos HLA en cardiopatas chagásicos: nueva evidencia basada en un análisis de casos y controles.

We studied the distribution of HLA, B and C antigens in 73 Chagasic subjects with and without heart disease. Both groups were matched for age, sex, birth place and history of family residence. Thirty two subjects without evidence of Chagasic infection, with and without heart disease and matched for the same variables were also studied. Compared to all other groups, a significant increase in the level of the B40 Cw3 antigen combination was found in Chagasic subjects without evidence of heart disease.

HLA antigens in Brazilian patients with paracoccidioidomycosis.

Eighty patients with paracoccidioidomycosis were typed for 43 HLA specificities from loci A, B, C and DR. A highly significant increased frequency of HLA-B40 (relative risk 29.2) and HLA-Cw1 (relative risk 8.8) were found in patients compared to control subjects. The frequencies HLA-A2, B7 and B21 were also increased in patients and haplotypes-B40-Cw1 and -A2-B40 were positively correlated with the disease. DR antigen frequencies were not significantly altered in the patients and evidence of a protective effect was not found for any of the 43 antigens tested. These findings further support the involvement of the HLA system in the genetic susceptibility to paracoccidioidomycosis and the importance of ethnic variability in this association.

HLA Gm systems and susceptibility to alcoholic cirrhosis: a study of mixed-race subjects.

The fact that only a small percentage of excessive drinkers develop cirrhosis may be due to a genetic susceptibility to the disease. In order to identify possible genetic risk factors for cirrhosis, we studied mixed-race (Negroid-Caucasian) inhabitants of the French West Indies and compared: (1) the frequency of 51 HLA-A, -B, -C and -DR antigens in 41 subjects with alcoholic cirrhosis and in two control groups consisting of 41 excessive drinkers free of liver disease and 51 healthy non-drinkers; and (2) the frequency of Gm and Km haplotypes in the same groups. Analysis of the Gm system also determined the patients' ethnic origins. The frequency of the HLA-A2 antigen was significantly higher in the cirrhotic patients than in the control group of excessive drinkers (chi 2 = 4.47; P less than 0.05), while that of the HLA-B15 antigen was significantly lower (chi 2 = 5.14; P less than 0.05). The frequency of the Cw4 antigen was significantly higher in the cirrhotics than in the non-drinkers (chi 2 = 5.59; P less than 0.05). However, these differences did not persist when the number of comparisons was taken into account. The frequency of Gm and Km haplotypes was not significantly different in the three groups. In conclusion, complementary studies are required to determine the value of the Gm-Km system as a marker of susceptibility to alcoholic cirrhosis. Our results do not identify an association between HLA antigens and cirrhosis specific to a negroid ethnic group and support the notion that such an association is weak.

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-10-year-old patients was 71%. 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 10 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% in the control group (p less than 0.05). 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.

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)

Anti HTLV-I antibodies and HLA phenotypes in the West Indies.

Sera of supposedly healthy blood donors were screened for the presence of anti HTLV-I p24 antibodies, and HLA typing for A, B, C and DR antigens was performed for 68 seropositive subjects and 92 seronegative controls. HLA phenotypes of the two groups were not significantly different but the level of the antibody response was related to the antigens of the HLA-B (P = 0.02) and -C loci (P = 0.003). Subjects with HLA-B12 or -B21 antigens had lower titres than the others. Subjects with HLA-Cw2 or -Cw7 antigens had higher titres than the others, but only the difference between HLA-B12 positive and negative subjects (P = 0.002) remained significant at the alpha = 0.10 level if the classical, although conservative, Bonferroni procedure was used to correct for the number of comparisons performed.

Are HLA class II genes controlling susceptibility and resistance to Brazilian pemphigus foliaceus (fogo selvagem)?

In order to investigate the possible association between Brazilian pemphigus foliaceus and HLA, we studied 48 patients and 74 matched controls, all Brazilian Caucasoids, for HLA-A,B,C; DR1 to DRw8 and DQw1 to DQw3. The frequencies of DR1, DR4 and B16 were significantly increased, while DR7 was significantly decreased among the patients. Furthermore DQw2, likewise the DR specificities associated with it - DR3 and DR7 - never occurred among the patients in the absence of the susceptibility markers DR1, DQw1 or DR4, DQw3. Acting on these findings, we suggest that at least two MHC-class II genes are involved in the pathogenesis of Brazilian pemphigus foliaceus: at least one gene, associated to DR1,DQw1 and to DR4,DQw3, confers susceptibility and at least one gene, associated to DR7,DQw2 and DR3,DQw2, confers resistance. The susceptibility gene(s) seem(s) to be epistatic to or dominant over (if allelic) the resistance gene(s). Both are dominant over other alleles at their locus (or loci).

HLA-A29 and genetic susceptibility to chromoblastomycosis.

The distribution of 12 HLA-A, 14 HLA-B, seven HLA-C, seven HLA-DR and three HLA-DQ antigens was determined in 32 non-consanguineous white Brazilians suffering from chromoblastomycosis and 77 healthy controls, matched for ethnic background, sex and age and living in the same geographical area. A significant difference between the two groups was seen only in respect to one HLA-A antigen: A29 was present in 28% of patients as opposed to 4% of the controls (P corrected = 0.03). This finding indicates that susceptibility to chromoblastomycosis may be influenced by a gene located on chromosome 6, in the region of the major histocompatibility complex. The relative risk for an HLA-A29 carrier to develop chromoblastomycosis was estimated as 10.

IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity.

Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.