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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).

Rheumatoid arthritis is a chronic and systemic autoimmune disease characterized by inflammation and destruction of the synovial joints. It affects approximately 0.5% of the Latin-American population and is three times more common in women than in men. Evidence of familial aggregation (lambdas=2-17) was the first indication of a genetic susceptibility to disease. As in other autoimmune diseases, it has a complex genetic basis. Results from whole-genome scans indicate that the HLA region contains a significant and consistent set of linked loci. However, HLA accounts for only one-third of the genetic susceptibility of disease, indicating that non-HLA genes are also involved in the disease susceptibility. In Latin-America, association with HLA-DRB1*0404 and TNF -308A alleles has been uniformly established; however, many other candidate genes remain to be studied. The identification of genetic factors conferring susceptibility to rheumatoid arthritis will contribute to the knowledge of the pathogenic mechanisms, ability to predict its occurrence, the development of diagnostic tools, prognosis, and treatment. The genetic epidemiology of rheumatoid arthritis is herein reviewed; a set of recommendations is provided for the design, analysis and interpretation of genetic association studies in the context of Latin-American populations.

Introduction: Pemphigus vulgaris (PV) is a rare autoimmune bullous disease that affects the skin and mucosae, characterized by the presence of antibodies against desmoglein 3, that causes acantholisis and formation of intraepidermal blisters. Observation of PV cases in several members of the same family suggests the existence of genetic factors that contribute to susceptibility to suffer the disease. However, very few cases of familial PV have been described. Based on its autoimmune nature, many studies have found an association between PV and the HLA class II allele, specifically with the HLA-DRB1*0402 DQB1*0302 and HLA-DRB1*1401 DQB1*0503 haplotypes that bestows a significant risk of disease., Objectives: Study of three families with PV., Patients and Methods: In this study, we present three families, with a total of 7 patients, diagnosed of familial PV. HLA antigens were determined with the PCR (polymerase chain reaction) technique in several members of these families., Results: All the subjects affected were positive for HLA DR4 and HLA DR14. The fact that different families with PV are associated with identical haplotypes and that healthy siblings of the patients have the same haplotype is of special interest., Conclusion: These results support the concept of genetic predisposition in this rare disease.

Background: Inherited susceptibility to type 1 diabetes is partially determined by HLA genes. HLA-DQA1 and DQB1 alleles have been chosen as the most sensitive susceptibility markers. Family studies are a good method to establish specific relationship between type 1 diabetes and specific haplotypes as risk markers for the disease., Aim: To analyse the role of class II HLA molecules and the distribution of haplotypes in the genetic predisposition to type 1 diabetes in Chilean families., Material and Methods: Twelve family groups constituted by 58 individuals were studied. Fourteen children (10 male) less than 15 years old with diabetes and their family members were included. The allele and haplotype frequency of the population was determined in 74 unrelated healthy children., Results: Risk haplotypes such as HLA-DR3/DQB1*0201/DQA1*0501 and HLA-DQB10302/DQA1*0501 were more common among diabetic patients and comparable to the haplotypes described in other Caucasian populations. Meanwhile, protective haplotypes found in relatives without diabetes, such as HLA-DR2/DQB1*0301/DQA1*0301 and HLA-DR8/DQB1*0402/DQA1*0301, were absent in children with diabetes., Conclusions: The general pattern of neutral or protective haplotypes, found with higher frequency in non diabetic individuals, indicates that their presence could confer protection against the disease, with a higher effect over those haplotypes associated to the disease.

Background: A study of the phenotype, activation and adhesive cells factors and cytokines in minor salivary glands in patients with primary Sjögren's syndrome (pSS), secondary Sjögren's syndrome (sSS) and autoimmune diseases (AD) without Sjögren's syndrome., Patients and Methods: We have studied the minor salivary glands in 30 patients with pSS, 30 patients with sSS, 19 patients with AD without SS and 18 controls, using immunohistochemical techniques to analyze the molecular expression of CD3, CD4, CD8, CD20, CD25, CD14, CD56, CD11a, CDw50 (ICAM-3), HLA-DR, IL-1, TNF-alpha and IFN-gamma in lymphocytic infiltration and epithelial cells., Results: Phenotype features were similar in patients with pSS and sSS, except that CD20+ lymphocyte expression was significantly higher in the sSS group (p = 0.023). The patients affected by AD without SS had activated lymphocytes in minor salivary glands in a similar manner to patients affected by pSS and sSS. No significant differences were found in HLA-DR expression in epithelial cells. We found unusual CD25 expression in epithelial cells in patients with SS but not in patients with AD without SS. The differences between pSS and sSS are related to SS theoretical time development and to immunosuppressive treatments., Conclusions: The immunohistochemical pattern of minor salivary glands is similar in patients with pSS and sSS. Patients with AD are likely to develop immunological changes in minor salivary glands attributable to activated lymphocytes.

The aim of this study was to analyze the variability of the HLA-II system in a series of patients with chronic hepatitis B, chronic hepatitis C and acute hepatitis B to know whether there is any relationship between the polymorphism of the HLA system, the different types of hepatitis and the evolution of the infection. HLA-II antigens were determined by a PCR technique in serum samples of 24 controls, 22 cases of chronic hepatitis C, 38 cases of chronic hepatitis B and 11 with acute hepatitis B. The prevalence of the HLA-DR4 antigen was lower in the cases of chronic hepatitis B (10.5%) and C (13.6%) than in the controls (33.3%), particularly the DRB1*0401 allele (p = NS). The prevalence of HLA-DR6 was similar in chronic hepatitis B (42.1%) and acute hepatitis B (45.5%). Predominance of the DRB1*1301 and DRB1*1302 alleles were, however, observed in acute hepatitis B (36.4%) versus chronic hepatitis B (13%). These data suggest that immunologic factors such as HLA antigens may influence in the susceptibility to infection by HBV and HCV. The use of PCR techniques which discriminate between the different alleles of the HLA antigens may provide better knowledge of the immune response.

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.

Background Aims: The effects of two anesthetic agents, alfentanil and isoflurane, on the macrophage-monocytic system and the relation with the adrenocortical-hypophyseal axis were analyzed., Material and Methods: Thirty ASA I-II patients submitted to elective surgery were distributed into two groups: group I, analgesic anesthesia with alfentanil 100 micrograms/kg, a perfusion of 2-3 micrograms/kg/min and naloxone 0.2-0.4 mg upon termination of surgery; group II, inhalation anesthesia with isoflurane at 2-2.5% and O2/air = 1/1. HLA-DR membrane receptors and vimentin threads of the cytoskeleton were determined in basal conditions, at one hour and two hours of induction and upon termination of surgery by means of indirect immunofluorescence with the use of monoclonal antibodies. Phagocytosis of latex particles was also measured and ACTH and cortisol levels were obtained by radioimmunoassay., Results: In group I (alfentanil) a decrease (p < 0.01) of all the monocyte parameters analyzed, which was more significant than that observed in group II (isoflurane), was observed. In group II only the expression of HLA-DR and the index of phagocytosis (p < 0.05) were statistically significant. Following the administration of naloxone a reversion of these parameters was observed. The maximum immune depression corresponded with the lowest values of ACTH and cortisol (group I) with surgical stress being discarded as the cause of this immunodepression., Conclusions: Alfentanil produces a monocytic depression which reverses following the administration of naloxone, thus discarding surgical stress as the cause of this immunodepression suggesting a mechanism mediated by opiate receptors. With regards to isoflurane, the functions of the mononuclear-phagocytic system were hardly altered in the patient studied.

The evaluation of the presence of p24 antigen on the membrane of peripheral blood mononuclear cells from 31 HIV infected individuals is presented. The study was performed by indirect immunofluorescence and flow cytometry and the data were analyzed by the Kolmogorov-Smirnov test. Values obtained [D/s(n)] result from the comparison of the fluorescence histograms of each sample with a control one. Cases showing p24 Ag on peripheral blood mononuclear cells also presented percentages of CD3, HLA-DR positive cells significantly higher than p24 negative ones. In addition, D/s(n) values were superior in symptomatic patients than in asymptomatic ones, which indicate the existence of a correlation between flow cytometry results, viral replication and clinical course. Nevertheless in this study, as well and in previous ones, a high degree of cross reactivity between the anti-p24 monoclonal antibody employed and normal lymphocytes has been observed. This reactivity is localized preferentially in the CD4 positive subset.

We evaluated in human monocytes the effect of high doses of alfentanyl on the expression of vimentin filaments, the phagocytic activity and the membrane display of HLA-DR molecules in the subjects undergoing surgery. The study was performed on 30 patients, ASAI-II. The patients received 100 mcg/kg i.v. of Alfentanil and the maintenance of anaesthesia was made with Alfentanil (2-3 mcg/kg/min.). The patients were randomized in two groups. The patients were ventilated with N2O:O2 (1:1) (Group I) or air: O2 (1:1) (Group II). After surgery, all patients of the Group II received Naloxone (0.2-0.4 mg). Central venous blood samples were obtained before induction, one and two hours after induction of anaesthesia and at the end of surgery. Separation of monocytes was performed according to Boyum technique. CD35 and HLA-DR molecules and vimentin filaments were studied by indirect immunofluorescence method using monoclonal antibodies. Percentage of positive cells were read with a cytofluorometer. The phagocytic function of monocytes was determined by ingestion of latex particles. Cortisol and ACTH plasma levels were determined by RIA. High doses of Alfentanyl depress phagocytic function and membrane display of CD35 and HLA-DR molecules in monocyte and induce marked changes in the organization of vimentin filaments in these cells in patients undergoing surgery. This monocytic depression was more marked in the patients ventilated with N2O. In our results there was uninhibition of ACTH and cortisol plasma levels responses to surgical stress by Alfentanil administration. Since the effects of Alfentanil were reversed by Naloxone, an opioid receptor mechanism seems to mediate these events.

The spontaneous expression of Class II molecules (HLA-DR) was studied in cultured thyrocytes obtained from patients with Graves Disease (n = 7), Hashimoto's Thyroiditis (n = 5), euthyroid nodular goiter, (n = 12), papillary carcinoma (n = 5), and laryngeal carcinoma (3 normal thyroid glands). If nodular goiters and papillary carcinoma are of autoimmune origin, as Graves Disease and Hashimoto's Thyroiditis, they should spontaneously express HLA-DR antigen on their cell surface as this has been considered one of the initial steps of autoimmunity. The study was performed using the cytotoxicity assay. Immediately after the thyroid glands were obtained, thyrocytes were labelled with 51-Cr and incubated overnight; the cells were destroyed by adding monoclonal antiHLA-DR antibody and rabbit complement. The cytotoxicity index (CI% + SD) which reflects 51-Cr release from lyzed cells was used to measure antigen expression. While Graves Disease's and Hashimoto's Disease's thyrocytes expressed HLA-DR in high proportion, normal thyrocytes and thyroid cells from other diseases did so in minimal proportion (28.12 +/- 10.71 vs 2.26 +/- 2.32, p < 0.001). These findings strongly suggest that nodular goiters and papillary carcinoma are not of autoimmune origin since they are unable to express HLA-DR on their cell surface. It is postulated that HLA-DR expression is the result of the influence of T lymphocytes previously sensitized to thyroid antigens.

Out of a group of 220 acute lymphoblastic leukaemias (ALL) with phenotypic study at diagnosis, 18 were selected on which sequential studies were performed due to relapse (15 cases) or to lack of achievement of complete remission (primary resistant ALL, 3 cases). The purpose of this study was to analyse the incidence and characteristics of the possible antigenic changes with regard to the diagnosis. Along with the classic markers, a panel comprised of 20 monoclonal antibodies against lymphoid and myeloid antigens was used. Major phenotypic changes (acquisition of myeloid antigens CD13 and CD33) were found only in one case amongst the relapsing ALL (7%). Seven other patients (47%) showed minor phenotyping changes, including: 1) acquisition or loss of antigens (2 cases); 2) changes in more then 50% of any antigen's expression (4 cases); 3) both (1 case). These results might suggest that antigenic changes are rather frequent in relapsing ALL; however, none of such changes modified in our experience the phenotypic diagnosis so any change of this last should be regarded as an exceptional event. The majority of these antigenic changes consisted of the loss of maturation antigens (CD20) or acquisition of early markers (TdT, HLA-DR) or activation markers (CD38); this would mean that the relapsing blast cells show a functional status of activation and proliferation, with a phenotype more immature than that of the diagnosis, thus explaining the poorer prognosis of the patients in relapse. No phenotypic changes were found in the primary resistant ALL, which may indicate the persistence of the original cell clone without any alteration.

The expression of HLA-DR antigens and their capacity to reduce nitroblue tetrazolium (NBT) have been evaluated in monocytes (Mo) from 28 patients with colorectal carcinoma (CCa) before antineoplastic treatment as well as in 29 normal control (NC). Simultaneously, circulating immune complexes (CIC) levels were studied in both groups. The results were expressed as the media of percentages. They show a decrease of Mo bearing HLA-DR (p less than 0.001 vs NC) and increase of MO with capacity to reduce NBT (p less than 0.001 vs NC). An increase of CIC levels in CCa compared to the NC (p less than 0.001) was also observed. We can postulate that the decrease in HLA-DR expression could be caused by the increase of toxic oxygen intermediates whose production was induced by CIC or tumoral antigens adherence.

The relationship between laryngocele and laryngeal carcinoma has already been well established. A distinct entity is the carcinoma arising from the ventricular saccule or a preexisting laryngocele showing a peculiar clinical behavior and pathological features. We present here a case of ventriculosaccular carcinoma of the larynx, discussing the clinical presentation and the immunohistochemical analysis performed using monoclonal antibodies, and the factors which might modulate the aggressiveness of the neoplasm.

The authors studied the expression of CD1 and HLA-Dr antigen in benign and malignant melanic tumors to known if were the melanoma's cells or Langerhans cells, presents on the tumor, which exhibited the HLA-Dr antigens, and if the HLA-Dr expression was related to volume, depth and metastatic characteristics. These antigens were studied with the monoclonal antibodies labelled to avidin-biotin-peroxidase system. The results shows than the proportion between the number of Langerhans cells and HLA-Dr positive cells is inverse. No differences were found between the expression of the HLA-Dr antigens and number of Langerhans cells and volume, depth or metastatic characteristics.