[High frequency of DQ8 in the celiac population of Chaco province, Argentina]. / Alta frecuencia de DQ8 en la población celiaca de la provincia del Chaco, Argentina.

BACKGROUND: There is a strong association between celiac disease (CD) and certain genes of the major histocompatibility complex (HLA). The CD specifically related alleles are those coding for HLA-DQ2 heterodimer and to a lesser degree for HLA-DQ8. OBJECTVE. The aim of this study was to evaluate the frequency of HLA-DQB1* and HLA-DRB1* alleles, haplotypes, and genotypes in patients diagnosed with CD and in control population of Chaco, in order to establish its distribution and compare it with that observed in other populations. METHODS: A total of 139 samples from patients diagnosed with CD and 119 healthy controls were typed for HLA-DQ and HLA-DR, using PCR and reverse hybridization (INNO-LiPA or Dynal). RESULTS: Comparing patients with CD vs. controls, the DQBI*0201 (P = 0.0002), DQBJ*0202 (P = 0.0046), DQBI*0302 (P = 0. 0006), DRBl *03 (P = 0.0002), DRBl *04 (P = 0.0199) and DRB1 *07 (P = 0.0062) were significantly increased, while a decrease was observed in HLA-DQB1*0301 (P = 0.0006), HLA-DQBI*0303 (P = 0.0070), DQBI*0501 (P = 0.0023), DQB1*0604 (P = 0.0140) DRB1*01 (P = 0.0023), DRB1*08 (P = 0.0165), DRB1*09 (P = 0.0362) and DRB1*16 (P = 0.0228). Within DQB1* genotypes associated with EC, 65.4% of patients had the DQB1*02 in linkage disequilibrium with DRB1*03 or DRB1*07 (DQ2), and 43.2% presented genotype DQB1*0302 in linkage disequilibrium with DRB1*04 (DQ8). Both genotypes were shared by 15.2% of them. CONCLUSIONS: We point out the high frequency of DQ8 associated with CD. Although the DQ2 is still the most common, this finding could be attributed to the Amerindian influence in our population.

[KIR-HLA class i and pulmonary tuberculosis in the Amerindian population in Chaco, Argentina]. / KIR-HLA clase i y tuberculosis pulmonar en población amerindia del Chaco, Argentina.

INTRODUCTION: The susceptibility to pulmonary tuberculosis (TB) is multifactorial, thus genetic factors such as HLA and immunoglobulins-like killer receptors (KIR) could be predisposed to the development of the disease. Aim To evaluate whether any HLA classi allele and its combination with KIR could be related to the development of TB in the Wichi Amerindian community in north-eastern Argentina. METHODS: A cohort study was conducted that included 18 families, 35 individuals affected with TB, 84 cohabiting families, and 63 controls of the same ethnic group. A and B loci of HLA classi were typed by generic PCR followed by reverse hybridization (Dynal), locus C by PCR-SSOP. KIR receptors were studied using sequence specific PCR. RESULTS: There was a highly significant association with allele B*35:19/47 in TB vs. household contacts [Pc=0.0051] and vs. controls [Pc=0.0033], and with allele HLA-C*03 in TB vs. household contacts [Pc=0.014] and vs. controls [Pc=0.0033]. KIR receptors had shown increased KIR2DL3/KIR2DL3 frequency in combination with the C1 group of HLA-C (P=.018). HLA-C*03 belongs to C1 group, and this combination could have a strong inhibitory action on the infected cell. CONCLUSION: HLA-B35:19/47-C*03 haplotype could be a susceptibility factor to TB and KIR2DL3-HLA-C1 combination have an inhibitory capacity on NK cells, and might contribute to the course of the infection by Mycobacterium tuberculosis.

Alta frecuencia de DQ8 en la población celiaca de la provincia del Chaco, Argentina. / [High frequency of DQ8 in the celiac population of Chaco province, Argentina].

BACKGROUND: There is a strong association between celiac disease (CD) and certain genes of the major histocompatibility complex (HLA). The CD specifically related alleles are those coding for HLA-DQ2 heterodimer and to a lesser degree for HLA-DQ8. OBJECTVE. The aim of this study was to evaluate the frequency of HLA-DQB1* and HLA-DRB1* alleles, haplotypes, and genotypes in patients diagnosed with CD and in control population of Chaco, in order to establish its distribution and compare it with that observed in other populations. METHODS: A total of 139 samples from patients diagnosed with CD and 119 healthy controls were typed for HLA-DQ and HLA-DR, using PCR and reverse hybridization (INNO-LiPA or Dynal). RESULTS: Comparing patients with CD vs. controls, the DQBI*0201 (P = 0.0002), DQBJ*0202 (P = 0.0046), DQBI*0302 (P = 0. 0006), DRBl *03 (P = 0.0002), DRBl *04 (P = 0.0199) and DRB1 *07 (P = 0.0062) were significantly increased, while a decrease was observed in HLA-DQB1*0301 (P = 0.0006), HLA-DQBI*0303 (P = 0.0070), DQBI*0501 (P = 0.0023), DQB1*0604 (P = 0.0140) DRB1*01 (P = 0.0023), DRB1*08 (P = 0.0165), DRB1*09 (P = 0.0362) and DRB1*16 (P = 0.0228). Within DQB1* genotypes associated with EC, 65.4

of patients had the DQB1*02 in linkage disequilibrium with DRB1*03 or DRB1*07 (DQ2), and 43.2

presented genotype DQB1*0302 in linkage disequilibrium with DRB1*04 (DQ8). Both genotypes were shared by 15.2

of them. CONCLUSIONS: We point out the high frequency of DQ8 associated with CD. Although the DQ2 is still the most common, this finding could be attributed to the Amerindian influence in our population.

Alta frecuencia de DQ8 en la población celiaca de la provincia del Chaco, Argentina / [High frequency of DQ8 in the celiac population of Chaco province, Argentina].

BACKGROUND: There is a strong association between celiac disease (CD) and certain genes of the major histocompatibility complex (HLA). The CD specifically related alleles are those coding for HLA-DQ2 heterodimer and to a lesser degree for HLA-DQ8. OBJECTVE. The aim of this study was to evaluate the frequency of HLA-DQB1* and HLA-DRB1* alleles, haplotypes, and genotypes in patients diagnosed with CD and in control population of Chaco, in order to establish its distribution and compare it with that observed in other populations. METHODS: A total of 139 samples from patients diagnosed with CD and 119 healthy controls were typed for HLA-DQ and HLA-DR, using PCR and reverse hybridization (INNO-LiPA or Dynal). RESULTS: Comparing patients with CD vs. controls, the DQBI*0201 (P = 0.0002), DQBJ*0202 (P = 0.0046), DQBI*0302 (P = 0. 0006), DRBl *03 (P = 0.0002), DRBl *04 (P = 0.0199) and DRB1 *07 (P = 0.0062) were significantly increased, while a decrease was observed in HLA-DQB1*0301 (P = 0.0006), HLA-DQBI*0303 (P = 0.0070), DQBI*0501 (P = 0.0023), DQB1*0604 (P = 0.0140) DRB1*01 (P = 0.0023), DRB1*08 (P = 0.0165), DRB1*09 (P = 0.0362) and DRB1*16 (P = 0.0228). Within DQB1* genotypes associated with EC, 65.4

of patients had the DQB1*02 in linkage disequilibrium with DRB1*03 or DRB1*07 (DQ2), and 43.2

presented genotype DQB1*0302 in linkage disequilibrium with DRB1*04 (DQ8). Both genotypes were shared by 15.2

of them. CONCLUSIONS: We point out the high frequency of DQ8 associated with CD. Although the DQ2 is still the most common, this finding could be attributed to the Amerindian influence in our population.

KIR-HLA-A and B alleles of the Bw4 epitope against HIV infection in discordant heterosexual couples in Chaco Argentina.

Activating and inhibitory killer immunoglobulin-like receptors (KIR) and their ligands HLA-Bw4 (loci A and B) were studied by way of establishing whether they can contribute to protection against HIV-1 infection in highly exposed and persistently seronegative (HESN) patients. Twenty-three HIV-1 serodiscordant heterosexual couples, 100 HIV-1(+) patients and 200 healthy individuals were included in this retrospective case-control study. HLA typing was performed by means of PCR followed by sequence-specific oligonucleotide probe reverse hybridization. KIR3DL1 and KIR3DS1 were studied by PCR sequence-specific primers. The frequency of KIR3DS1(3DS1/3DL1)-Bw4 combination was significantly higher in HESN patients versus the discordant couples (P = 0·0003) and HIV-1(+) patients (P = 0·0001). Conversely, the KIR3DL1/KIR3DL1 homozygosity was significantly decreased in HESN patients versus the discordant couples (P = 0·00003), and HIV-1(+) patients (P = 0·00066). The frequency of HLA-A*32 and HLA-B*44 was higher in HESN versus their discordant couples (P = 0·009; P = 0·049), and HIV-1(+) patients (P = 0·00002; P = 0·0001). This had greater significance in combination with KIR3DS1 (3DS1/3DL1). KIR3DS1(3DS1/3DL1) could have a greater effect on protection against HIV-1 infection in HESN patients when bound to a specific HLA allele, in this case HLA-A*32 and HLA-B*44, both Bw4 alleles. The differences probably arise both in the HLA alleles and in the subtypes of KIR receptors depending on the ethnic group studied.

[Role of HLA-DR and HLA-DQ alleles in multibacillary leprosy and paucibacillary leprosy in the province of Chaco (Argentina)]. / Papel de las moléculas HLA-DR y HLA-DQ en la lepra multibacilar y paucibacilar en la provincia del Chaco; Argentina.

OBJECTIVES: Segregation analyses in several populations have suggested a relationship between specific human leukocyte antigen (HLA) class II alleles and the development of different types of leprosy. The aim of this study was to determine the frequency of HLA class II DR and DQ alleles among leprosy patients in Chaco province, northeast Argentina, in an effort to determine whether these alleles might be involved in the development of the multibacillary (MB) and paucibacillary (PB) forms of leprosy. PATIENTS AND METHODS: Samples from 89 leprosy patients (MB = 70, PB = 19) and 112 healthy control subjects were analyzed. The HLA-DRB1 and HLA-DQB1 alleles were determined by PCR amplification and reverse hybridization with sequence-specific oligonucleotide probes, and analyzed with the INNO-LiPA typing system and LiPA software. DQB1*0201/0202/0203 in patients with MB leprosy and DRB1*04 in patients with PB leprosy were detected at significantly lower frequencies as compared with the normal controls. RESULTS: These data indicate that DQB1* 0201/0202/0203 may be a protective factor in MB leprosy and DRB1*04 in PB leprosy. DISCUSSION: We attribute the differences between our findings and those of other authors to the fact that the Caucasian inhabitants of Chaco include a considerable mixture of South American natives (Guaraníes and Tobas).

HLA class II involvement in HIV-associated Toxoplasmic encephalitis development.

UNLABELLED: A total of 220 individuals were included in this study, 112 HIV-seronegative healthy individuals and 108 HIV-1-infected patients involving: 18 AIDS patients with Toxoplasmic encephalitis (AIDS-TE), 49 AIDS patients without TE, and 41 asymptomatic patients, were genotyping for DR and DQ loci by molecular biology techniques. Fisher's Exact test was used for statistical analysis. HLA-DQB*0402 and DRB1*08 alleles were associated with a high risk to develop opportunistic infections with neurological involvement, mainly Toxoplasma encephalitis in relationship with subjects healthy (OR = 20.43; Pc = 7.0 x 10(-6) and OR = 11; Pc = 2.6 x 10(-4), respectively); in relationship with AIDS no TE (OR = 6.98; Pc = 0.028 and OR = 4.85; P = 0.012, Pc = 0.14) and with patients in asymptomatic stage (OR = 61.50, Pc = 8.4 x 10(-6) and OR = 19.38; Pc = 3.9 x 10(-4)), respectively. CONCLUSIONS: It was concluded that the presence of HLA-DQB*0402 and DRB1*08 alleles in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasmic encephalitis.

Association of HLA-DQ and HLA-DR alleles with susceptibility or resistance to HIV-1 infection among the population of Chaco Province, Argentina.

The pathogenesis of infections clearly involves immunoregulatory host factors and products of Major Histocompatibility Complex (MHC) genes class II which present antigenic peptides to the T-cell receptor on CD4+ cells which in turn increase the production of specific antibodies and cytotoxic T lymphocytes. The objective of this study was to determine the frequency of the different alleles of HLA class II DQ and DR in HIV-1 infected patients of Caucasians with Guaraní and Toba genetic backgrounds in an effort to determine the prevalence of certain alleles which could signify a factor of susceptibility to or protection against HIV-1 infection. A total of 54 HIV-1 positive patients and 46 healthy control subjects participated in the HLA-DQB1 study while 54 HIV-1 (+) patients and 57 healthy controls were analyzed for HLA-DRB1. Both HLA-DQB1 and HLA-DRB1 genotyping were performed using PCR and sequence-specific reverse hybridization oligonucleotide probe and analyzed with the LiPA Key Typing System and LiPA software. HLA-DQB1*0203(P = 0.041) and DRB1*01(P = 0.05) exhibited a decreased frequency in HIV-1 (+) patients while HLA-DRB1*13 (P = 0.017) was observed more frequently. Several studies have reported different findings, depending on the populations analyzed. Our data show that there are HLA class II alleles associated with susceptibility or resistance to HIV-1 infection and that these differ among ethnic groups. We believe that our results differ from the other Caucasians populations due to the ethnic variability of Chaco inhabitants resulting from mixing between Caucasians and South American natives (Guaraníes and Tobas).

Association of HLA-DQ and HLA-DR alleles with susceptibility or resistance to HIV-1 infection among the population of Chaco Province, Argentina.

The pathogenesis of infections clearly involves immunoregulatory host factors and products of Major Histocompatibility Complex (MHC) genes class II which present antigenic peptides to the T-cell receptor on CD4+ cells which in turn increase the production of specific antibodies and cytotoxic T lymphocytes. The objective of this study was to determine the frequency of the different alleles of HLA class II DQ and DR in HIV-1 infected patients of Caucasians with Guaraní and Toba genetic backgrounds in an effort to determine the prevalence of certain alleles which could signify a factor of susceptibility to or protection against HIV-1 infection. A total of 54 HIV-1 positive patients and 46 healthy control subjects participated in the HLA-DQB1 study while 54 HIV-1 (+) patients and 57 healthy controls were analyzed for HLA-DRB1. Both HLA-DQB1 and HLA-DRB1 genotyping were performed using PCR and sequence-specific reverse hybridization oligonucleotide probe and analyzed with the LiPA Key Typing System and LiPA software. HLA-DQB1*0203(P = 0.041) and DRB1*01(P = 0.05) exhibited a decreased frequency in HIV-1 (+) patients while HLA-DRB1*13 (P = 0.017) was observed more frequently. Several studies have reported different findings, depending on the populations analyzed. Our data show that there are HLA class II alleles associated with susceptibility or resistance to HIV-1 infection and that these differ among ethnic groups. We believe that our results differ from the other Caucasians populations due to the ethnic variability of Chaco inhabitants resulting from mixing between Caucasians and South American natives (Guaraníes and Tobas).

Anticuerpos anticitoplasma de neutrofilos (ANCA) en pacientes infectados por HIV sintomaticos y asintomaticos / Anti-neutrophil cytoplasmic antibodies (ANCA) in patients with symptomatic and asymptomatic HIV infection

Es conocido que en la etiopatogenia del Síndrome de Inmunodeficiencia Adquirida (SIDA) no sólo interviene el efecto citopático del virus sobre la población CD4, sino que también se activan otros complejos mecanismos entre ellos los de tipo autoinmune. El objetivo del trabajo fue estudiar en 88 pacientes HIV (+) (49 asintomáticos y 39 sintomáticos) los anticuerpos anticitoplasma de los neutrófilos (ANCA), a fin de correlacionarlos con algunos de los cuadros clínicos más frecuentes. Se utilizó la técnica de inmunofluorescencia indirecta (IFI) sobre improntas de polimorfonucleares (PMN). Se observó que la presencia de ANCA fue más frecuente en el grupo de enfermos (53,8 por ciento) respecto de los portadores asintomáticos (4,1 por ciento). Dentro del grupo ANCA (+) se observó correlación con infección pulmonar (95,9 por ciento), siendo la tuberculosis (TBC), la causa más frecuente de ésta. Cuando se comparó la presencia de ANCA en el grupo TBC(+) HIV(+) con el grupo TBC(+) HIV(-), se observó que los ANCA positivos se asociaban al primer grupo en forma significativa. Se cree que la presencia de estos anticuerpos puede estar relacionada con mecanismos de tipo autoinmune determinados por la expresión inadecuada de ciertas proteínas blanco tales como la mieloperoxidasa o proteinasa 3. La presencia importante de ANCA en pacientes HIV sintomáticos con infección pulmonar por Mycobacterium tuberculosis y no asi en pacientes HIV(+) asintomáticos o en pacientes con TBC pulmonar sin infección con HIV, parecería indicar que ni el virus per se, ni la infección pulmonar serían los responsables directos de la producción de estos anticuerpos. (AU)

Anticuerpos anticitoplasma de neutrofilos (ANCA) en pacientes infectados por HIV sintomaticos y asintomaticos / Anti-neutrophil cytoplasmic antibodies (ANCA) in patients with symptomatic and asymptomatic HIV infection

Es conocido que en la etiopatogenia del Síndrome de Inmunodeficiencia Adquirida (SIDA) no sólo interviene el efecto citopático del virus sobre la población CD4, sino que también se activan otros complejos mecanismos entre ellos los de tipo autoinmune. El objetivo del trabajo fue estudiar en 88 pacientes HIV (+) (49 asintomáticos y 39 sintomáticos) los anticuerpos anticitoplasma de los neutrófilos (ANCA), a fin de correlacionarlos con algunos de los cuadros clínicos más frecuentes. Se utilizó la técnica de inmunofluorescencia indirecta (IFI) sobre improntas de polimorfonucleares (PMN). Se observó que la presencia de ANCA fue más frecuente en el grupo de enfermos (53,8 por ciento) respecto de los portadores asintomáticos (4,1 por ciento). Dentro del grupo ANCA (+) se observó correlación con infección pulmonar (95,9 por ciento), siendo la tuberculosis (TBC), la causa más frecuente de ésta. Cuando se comparó la presencia de ANCA en el grupo TBC(+) HIV(+) con el grupo TBC(+) HIV(-), se observó que los ANCA positivos se asociaban al primer grupo en forma significativa. Se cree que la presencia de estos anticuerpos puede estar relacionada con mecanismos de tipo autoinmune determinados por la expresión inadecuada de ciertas proteínas blanco tales como la mieloperoxidasa o proteinasa 3. La presencia importante de ANCA en pacientes HIV sintomáticos con infección pulmonar por Mycobacterium tuberculosis y no asi en pacientes HIV(+) asintomáticos o en pacientes con TBC pulmonar sin infección con HIV, parecería indicar que ni el virus per se, ni la infección pulmonar serían los responsables directos de la producción de estos anticuerpos.