HLA-DRB1 alleles in Egyptian children with systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is an autoimmune disease characterized by multisystem organ damage due to autoantibody production. Polymorphism in genes at the Major histocompatibility complex [MHC] region represents an important susceptibility factor for SLE, especially HLA-DRBI and HLA-DQB1. Moreover; it was noted that ethnicity has a significant role in both disease susceptibility and disease expression. This work was planned out to study HLA-DRBI alleles association with SLE susceptibility and clinical presentations in Egyptian children with juvenile onset SLE. HLA-DRBI allele typing was done using polymerase chain reaction-sequence-specific oligonucleotide probe for 65 juvenile SLE patients and compared to 150 healthy controls of the same ethnic group. P values were corrected for the number of the alleles tested [Pc]. HLADRB1 asterisk 15 allele was significantly increased in SLE children Vs controls [OR=3.44; 95%CI=1.51-7,83; P=0.004 and Pc=0.048]. No HLA-DRB1 allele was found to be statistically significantly associated with renal, musculoskeletal, cutaneous, hematologic, cardiac or neuropsychiatric manifestations in children with SLE [P>0.05]. Although HLADRB1 asterisk 15 [15g] allele may be a susceptibility allele in Egyptian children with juvenile SLE; however HLA-DRB1 alleles do not contribute to SLE clinical presentations in these children

Immunohistochemical detection of dentritic cells in basal cell carcinoma of head and neck

Histogenesis of B.c.c. remains unclear, some investigators suggested that it arises from pluripotential immature epidermal cells which may differentiate in several directions to produce a variety of patterns, consequently it may be multicentric in origin. Twenty five cases of basal cell carcinoma of the head and neck region were studied. HLA-DR antigen expression was associated to some extent to degree of cell differentiation, and the depth of the tumor not with the histological subtypes of basal cell carcinoma. Detection of langerhans cells among less infiltrative be lal cell crcinoma confirm their possible role in the efficiency c he host immune response

Association of HLA-*08:DRB1*03 with immunoglobulin A-deficiency.

OBJECTIVE: Susceptibility to IgA deficiency (IgAD) is strongly associated with alleles of HLA, but it is not equally strong in different human populations. Therefore, the goal of this study was to determine the HLA-A, -B and -DRB1 antigenic and haplotypic frequencies in unrelated Polish Caucasian IgA-deficient patients who had never been examined so far in this respect. METHODS: The HLA alleles were determined by means of low resolution polymerase chain reaction with sequence specific primers (PCR-SSP) method in a group of IgA-deficient patients and control subjects from the same area. RESULTS: The HLA-DRB1*03 allele showed the strongest association with IgA deficiency in the Polish population (OR=6.6, p cor=0.0084). The HLA-B*08 allele was also associated with predisposition to the disease (OR=6.22, p cor=0.033). These significant associations could be explained in the context of a positive association of IgAD with the HLA-B*08:DRB1*03 haplotype, previously reported in other Caucasoid populations from Northern and Central Europe. In our group the HLA-B*08:DRB1*03 haplotype was present in 52.9% of IgA-deficient patients comparing to 9.9% in controls (p< 0.00011). A positive association of HLA-B*08 and DRB1*03 was stronger in IgA-deficient males than in females from the same group. CONCLUSION: Immunoglobulin A deficiency in Polish population is strongly associated with HLA-B*08:DRB1*03 haplotype rather than with single alleles.

Relato de caso: diabetes Flatbush - da cetoacidose ao tratamento não-farmacológico / Case report: diabetes Flatbush - from ketoacidosis to non pharmacological treatment

Um subgrupo de pacientes, em sua maioria negros ou hispânicos e obesos, tem a cetoacidose diabética (CAD) como forma de apresentação de diabetes mellitus (DM), mas, devido à sua evolução clínica, posteriormente é classificado como DM tipo 2. Estes indivíduos têm pesquisa de auto-anticorpos anti-GAD, anti-IA2 e anti-insulina negativa, mas freqüentemente em associação com HLA classe II de risco para DM tipo 1 (DRB1*03 e/ou DRB1*04). Este subtipo peculiar de DM é denominado diabetes flatbush. Neste artigo, relatamos o caso de uma paciente de origem caucasiana com tais características, na qual foi possível retirada da insulinoterapia. Os possíveis fatores associados a esta evolução favorável serão discutidos.

A subgroup of patients presents diabetic ketoacidosis at the onset of diabetes mellitus (DM) but later is classified as type 2 DM based on the clinical follow-up. These individuals, most commonly obese of African or Hispanic origin, have negative auto-antibodies associated with type 1 DM, but frequently HLA class II DRB1*03 and/or DRB1*04 are detected. This peculiar subtype of DM is commonly referred to as diabetes flatbush. Here we report the case of a Caucasian patient that exhibited the described evolution and in whom it was possible to withdraw insulin therapy. The possible factors associated with this favorable development are also discussed.

Human Leukocyte Antigen Typing Proficiency Surveys in Korea, 2005-2006 / 대한진단검사의학회지

BACKGROUND: To monitor the performance of histocompatibility testing laboratories, HLA proficiency survey in Korea has been conducted biannually since 1996. In this report, we summarized the results of the surveys performed in recent two years (2005-2006). METHODS: A total of four proficiency surveys were performed, in which 59-61 laboratories participated. Each survey included three tests for HLA class I (serology and DNA) and class II (DNA) typing and six tests for HLA crossmatch. RESULTS: The overall concordance of serologic typing was 98.9% (355/359) for HLA-A, 97.5% (350/ 359) for HLA-B, and 94.7% (337/356) for HLA-C. The antigens assigned correctly by less than 95% of the participating laboratories were A26 (93.8%), B38 (94.2%), Cw3/Cw10 (90.9%), Cw6 (94.4%), and Cw8 (74.3%). The overall concordance rates of DNA typing were 99.6% (533/535) for HLA-A, 99.8% (539/540) for HLA-B, and 100% (392/392) for HLA-C. Correct assignment of HLA-DRB1 and -DQB1 was reported by 99.2% (98.1-100%) and 96.7% (88.9-100%) for the generic level and 100% and 95.8% (75-100%) for the allelic level, respectively. On the average 3.8% (0-7.7%) of the total laboratories showed unacceptable results in the crossmatch tests. CONCLUSIONS: The rates of correct antigen identification and of unacceptable crossmatch were similar to those of previous surveys, which were considered satisfactory. The Korean proficiency survey program may have contributed to a high quality of HLA tests today and should be continued for further improvements of the tests tomorrow.

T lymphocyte activation and expression of costimulatory molecules in filarial elephantiasis

This study was carried in 48 patients with positive blood films for W. bancrofti microfilaria and 12 cross matched healthy control persons. All the studied cases were submitted to flow cytometric analysis of peripheral blood mononuclear cells using monoclonal antibodies against CD3, CD4, CD8, CD28, HLA-DR. In this study, there was a significant decrease in CD3 and CD4 T lymphocytes but the changes in CD8 T cells and CD28 expression on CD8 T lymphocytes was insignificant while the activation marker HLA-DR expression on CD4 T lymphocytes was increased

T-lymphocytes activation and expression of costimulatory molecules in human toxoplasmosis during pregnancy

The study was carried on 48 pregnant patients with positive sera for Toxoplasma antibodies [IgG, IgM] and 12 cross matched healthy control pregnant women. All studied cases were submitted to flow cytometric analysis of peripheral blood mononuclear cells [PBMNCs]; using monoclonal antibodies [MAbs] against CD3, CD4, CD8, CD28 and HLA-DR. Results revealed that, there was a significant decrease in CD4 and the expression of co stimulatory molecule CD28 on CD8 T lymphocytes, while the activation marker HLA-DR expression on CD4 T lymphocytes was significantly increased, but the changes in CD3 and CD8 T lymphocytes were insignificant

Relation between T lymphocytes activities and the intensity of schistosoma mansoni infection

This study was done on 60 schistosome patients and 12 cross matched healthy control persons. The schistosome patients were classified on the bases of intensity of infection into: 22 patients with light infection [one to 100 eggs/gm stool], 24 patients with moderate infection [101- 400 eggs/gm stool], 14 patients with heavy infection [>400 eggs/gm stool]. All the studied cases were submitted to flow cytometric analysis of peripheral blood mononuclear cells using monoclonal antibodies against CD3, CD4, CD8, CD28, HLA-DR. It was found that there was a significant decrease in CD3, CD4 and the expression of costimulatory molecule CD28 on CD8 T lymphocytes, while CD8 T lymphocytes and the activation marker HLA-DR expression on CD4 T lymphocytes were increased. These changes were more obvious with the increase in intensity of infection

combination of autoantibodies to cyclic citrullinated peptide [CCP] and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis

Antibodies against cyclic citrullinated peptide [CCP] and rheumatoid factors [RFs] have been demonstrated to predate the onset of rheumatoid arthritis [RA] by months or years. A nested case- control study was performed to analyse the presence of shared epitope [SE] genes, defined as HLA-DRB1-0404 or DRBI-0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified months before the onset of symptoms. Patients have family history of rheumatoid arthritis and recurrent arthralgia. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified, with a median antedating time of 6 months before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17-42% and 94%, respectively. In a logistic regression analysis, SE [odds ratio [OR] = 2.35], anti-CCP antibodies [OR 15.9], and IgA-RF [OR 6.8] significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR [66.8, 95% confidence interval 8.3-539.4] in predicting RA, compared with anti-CCP antibodies without SE [OR = 25.01, 95% confidence interval 2.8-222.2] or SE without anti-CCP antibodies [OR 1.9, 95% confidence interval 0.9-4.2]. This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA

Determination of laboratory reference ranges for lymphocyte immunophenotype subsets in healthy adult Japanese using flow cytometry.

This study represents a comprehensive evaluation of normative values for lymphocyte immunophenotype subsets using flow cytometry techniques in a Japanese population. Lymphocyte reference ranges were determined for percentage and absolute count of T, B, and NK cells in healthy adult Japanese using an extensive two-color immunophenotyping panel and consistently applied quality control methodology. Reference values were also determined for activation markers on CD3+ lymphocytes CD3+/CD25+, CD3+/CD38+ and CD3+/HLA-DR+. Differences in age and gender were observed for specific lymphocyte subsets. Comparison of the Japanese study with a Thai multi-center study that used similar methodology also demonstrated ethnic differences in lymphocyte reference ranges. The results in this study strongly suggest that reference values derived from studies in one population may not be applied to another population even when similar protocols for reagents, instruments and procedures are used although such studies do appear useful for epidemiological comparisons.

Inmunodepresión secundaria a traumatismo encefalocraneano / Immunodepression induced by traumatic brain injury

Introducción: Los pacientes que sobreviven a la injuria inicial por trauma severo presentan con elevada frecuencia complicaciones infecciosas, sépticas y disfunción multiorgánica. El traumatismo de cráneo (TEC) parece ser un factor de riesgo independiente en relación con la aparición de esas complicaciones. Los mecanismos causales estarían relacionados a una parálisis de la inmunidad celular inducida por el TEC. Objetivos: Analizar el grado de alteración de la competencia inmunológica en pacientes con TEC severo, determinado por los niveles plasmáticos de las citokinas IL-10, IL-6 y TNF-Ó y el nivel de expresión de HLA-DR de los monocitos sanguíneos CD14+. Pacientes y métodos: Se incorporaron 15 pacientes ingresados con TEC severo (GCS ¾ 8). Ninguno de los pacientes había recibido corticoides ni catecolaminas. Trece voluntarios normales se utilizaron como controles...

Some immunological studies and HLA-DRB1 in hepatitis C virus-related necrolytic acral erythema

Necrolytic acral erythema [NAE] is unique in its acral location and strong association with hepatitis C virus [HCV] and altered immunological junctions. The aim of the present work was to evaluate HLA DRB1 alleles and association of some parameter of immune system functions [complements C3 and C4, antismooth muscle antibody [ASMA] and antinuclear antibody [ANA] in NAE. Response of cutaneous lesion to low dose interferon alpha [3 million unit [MU] / week] and hydroxychloroquine was also evaluated. This study included 22 patients with HCV- related NAE [group I], 45 chronic hepatitis C without NAE [group II as pathological controls] and 45 healthy subjects [group III, normal controls]. ANA was positive more in patients than normal controls [18.2% vs 0%, P <0.003], however no significant difference was seen between patients groups. ASMA was positive significantly more in patients with NAE than HCV patients, and in both patients groups than normal controls 59.1%, 17.3% and 0%; P<0.001 and 0.0001 respectively]. A significant decrease in C3 and C4 was found in NAE patients than HCV patients without NAE, [P<0.01] and in both patients groups than normal controls [P<0.001]. NAE was associated with HLA -DRB1 03, [77.7%, 16 of 22 vs 24.2%, 11 of 45 of normal controls, Pc <0.0009 and 35.6% 16 of 45 HCV patients without NAE, Pc=0.03. Clinical improvement and significant decrease in ALT [P<0.001] was observed in NAE patients after two months of interferon alpha and hydroxychloroquine therapy. Necrolytic acral erythema [NAE] appears to be an immune mediated response in chronic HCV patients, associated with, lower C3 and C4 and higher frequency of positive ASMA. The results suggest that the development of HCV related ANE is associated with HLA-DRB1 03 marker. And low dose interferon alpha [3 MU per week] and hydroxychloroquine are good treatment modalities for NAE

Cellular phenotypes and immunity in acquired aural cholesteatoma

Middle ear cholesteatoma is characterized by the presence or a keratinizing squamous epithelium with proliferative features and associated with marked bone destruction. Aims of this study to detect the cellular phenotypes and their immunological functional state in aquired aural cholesteatoma. So, cellular membranous expression of CD4, CD8 and HLA-DR antigens on the infilterated mononuclear cells in cholesteatoma were studied through immunohistochemical method. Nine formalin-fixed cholesteatoma specimens were obtained from patients of chronic otitis media during their ear surgery. The patients' ages ranged between 11 to 43 years [mean age=22 yrs. and SD +/- 6.5] and they involved 15 males and 12 females. All patients had dry ears with no signs of bacterial infections for at least 2 weeks preoperatively. Also, three normal skin specimens from external auditory canals of these patients were taken as a control. All tissue specimens were subjected to Hematoxylin and Eosin staining and immunohistochemical [strept-avidin-peroxidase] method staining. The results showed CD4 positive [=T- helper or inducer] lymphocytes in 24 out of 27 specimens [88.8%] with subepithelial distribution and at the periphery of lymphoid follicles in 15 cases [55.5%].While, CD 8 positive [=T-suppressor or cytotxic] lymphocytes were seen only in 6 out of 27 specimens [22.2%] with diffuse distribution pattern. On the other hand, HLA-DR expression was observed in both cholesteatoma matrix and perimatrix cellular components indicating their immunocompetent activity. Keratinocytes of cholesteatoma matrix were HLA-DR positive in 18 specimens [66.6%] while, "epidermal Langerhans" cells were positive in 12 specimens [44.4%]. In the perimatrix of all specimens, infilterated lymphocytes and macrophages were positive for HLA-DR expression. Also, [either intact or degranulated mast cells] were demonstrated in all specimens scattered in the cholesteatoma perimatrix. Active T-helper cells are directly correlated to the expression HLA-DR has a certain playing. Role in epithelial proliferation and participating in bone resorption rather than cytotoxic T-lymphocytes. Also, activated keratinocytes and Langerhans' cells and sensitized mast cells contribute to the biologic features of cholesteatoma

Determinacion por PCR de la asociacion entre antigenos HLA clase II y penfigo vulgar / PCR determination of an association between class II HLA and pemphigus vulgaris

El pénfigo vulgar (PV) es una enfermedad cutaneomucosa que se caracteriza por la presencia de autoanticuerpos dirigidos contra la desmogléína 3, causando acantolisis y formación de ampollas. En el presente estudio se analiza la asociación de los antígenos HLA DR y HLA DQ en 30 pacientes caucásicos argentinos que padecen esta enfermedad comparada con una población control (N = 199) del mismo grupo étnico. La técnica utilizada fue PCR SSO. Los resultados muestran una asociación con HLA DR 4 (RR = 3.80, P = 0.001) y HLA DR 14 (RR = 5.97, P = 0.0001). En el caso de los subtipos moleculares DrBeta1 y DQBeta1, los que están positivamente asociados con PV pertencen a 2 alelos diferentes, tal como en otras poblaciones. El primero es DRBeta1 0402 (RR = 44.70, P = 10.7) y DQBeta1 0302 (RR = 71.82, P = 10.7) y el segundo es DRBeta1 1401 (RR = 117.94, P = 10.7) y DQBeta1 0503 (RR = 86.95, P = 10.7).

Análise comparativa da determinaçäo de antígenos HLA-DR por métodos sorológicos e por PCR-SSP / Comparative analysis of the HLA-DR antigen determination by serologic methods and by PCR-SSP

O objetivo deste trabalho foi comparar a determinaçäo dos antígenos HLA-DR por sorologia, utilizando-se A) anti-soros policlonais ou B) anticorpos monoclonais, com a determinaçäo em nível de DNA em amostras de sangue de receptores e doadores de rim e medula óssea. Observamos que os anticorpos monoclonais apresentam maior concordância com o PCR-SSP. Podemos concluir que as determinaçöes sorológicas têm menor precisäo, acarretando aproximadamente 48 por cento de imprecisoes com anti-soros policlonais e 21 por cento com anticorpos monoclonais. O PCR-SSP permite melhor definiçäo da compatibilidade HLA-DR entre receptor e doador, o que será, em última análise, adjuvante de melhor sobrevida do enxerto.