Enhanced HLA-DR expression on T-lymphocytes from patients in early stages of non-surgical sepsis / Elevada expresión de HLA-DR en linfocitos T de pacientes en fases tempranas de sepsis no quirúrgica

Introduction: Early detection of sepsis is a critical step to improve patient's survival and cellular markers effective diagnosis tools. The aim of this work was to evaluate HLA-DR expression on peripheral T-lymphocytes (CD3+), a marker associate to T-cell activation, as an early sepsis detection tool. Patients and methods: A cross-sectional study was conducted in twenty-six patients with confirmed sepsis by blood culture, eighteen healthy individuals and four patients with systemic inflammatory response syndrome. The analysis of the HLA-DR expression was carried by flow cytometry. Results: The patients with confirmed sepsis had significantly higher percentage of CD3+/HLA-DR+ lymphocytes compared with both, patients with SIRS (20.37±9.42 vs. 8.7±2.9; p<0.005) and healthy individuals (20.37±9.42 vs. 6.58±3.89; p<0.005). Moreover, the average amount of HLA-DR expressed was higher when caused by gram-positive than by gram-negative bacterias (216.61±131.35 vs. 135.05±31.82; p=0.041). A ROC curve analysis showed the utility of HLA-DR expression on T-cells to identify patients with sepsis. Discussion: Our results suggest that surface expression of HLA-DR on T-lymphocytes could be an early marker for the presence of sepsis in non-surgical septic patients

Introducción: La detección temprana de la sepsis es un paso crítico para mejorar la supervivencia del paciente. Nuestro objetivo fue evaluar la expresión de HLA-DR en linfocitos T periféricos (CD3+), marcador asociado a la activación de células T, como herramienta de detección temprana de la sepsis. Pacientes y métodos: Se realizó un estudio en 26 pacientes con sepsis confirmada, 18 sanos y 4 con síndrome de respuesta inflamatoria sistémica(SIRS). La expresión de HLA-DR se midió por citometría de flujo. Resultados: Los pacientes con sepsis tenían un porcentaje significativamente mayor de linfocitos CD3+/HLA-DR+ en comparación con los otros grupos, pacientes con SIRS (20,37±9,42 vs. 8,7±2,9; p<0,005) y sanos (20,37±9,42 vs. 6,58±3,89; p<0,005). La cantidad media de HLA-DR fue mayor cuando la sepsis estaba causada por bacterias gram-positivas que por gram-negativas (216,61±131,35 vs. 135,05±31,82; p=0,041). El análisis mediante curva ROC mostró la utilidad de la expresión de HLA-DR en células T para identificar pacientes con sepsis. Discusión: Nuestros resultados sugieren que la expresión de HLA-DR en linfocitos T podría ser un marcador temprano de sepsis en pacientes sépticos no quirúrgicos

[Two faces of an illness: rheumatoid arthritis followed by ankylosing spondylitis]. / Egy betegség két arca: szeronegatív rheumatoid arthritist követoen kialakuló spondylarthritis ankylopoetica--Esetbemutatás a 20 éves reumatológiai osztály anyagából.

Author presents the clinical history of a 35 years old female patient, who suffered from seronegative rheumatoid arthritis at the age of 29. Remission of the illness was followed by successful gravidity. Almost two years later spondylarthritis was diagnosed, showing only axial symptoms. The major histocompatibility complex analyzed by normal serological methods revealed the HLA B27 haplotype, typical for ankylosing spondylitis, and the HLA DR1 haplotype, typical for rheumatoid arthritis. During the examination of HLA DRB polymorphism, presence of DR B1 0101 allele was found, that plays role in the pathophysiology of rheumatoid arthritis. This case proves that a combination of HLA alleles typical for ankylosing spondylitis and rheumatoid arthritis can be found in the same patient.

Incidence of juvenile idiopathic arthritis in children in Estonia: a prospective population-based study.

OBJECTIVE: To study the incidence rate of juvenile idiopathic arthritis (JIA) and its clinical subtypes in Estonia, to follow the course of the disease in newly diagnosed patients for 2 years, and to find the frequency of human leucocyte antigens (HLA) B27, DR1 and DR4 in JIA patients. METHOD: A population-based study involving prospective registration of new cases of JIA in 1998-2000 and their clinical follow-up for 2 years. RESULTS: In 1998-2000, 162 new cases of JIA were diagnosed. The mean annual incidence rate of JIA was 21.7 per 100 000 children aged 0-15 years (22.9 in girls and 19.3 in boys). During the investigation period, the incidence rate rose 3.5-fold. Oligoarthritis was the most frequent subtype (mean annual incidence rate of 11.7 per 100 000), followed by seronegative polyarthritis (4.4 per 100 000). HLA-DR1, B27 and DR4 were found respectively in 44.4, 28.6 and 11.1% of cases in which the analysis was performed. In HLA-B27-positive patients, inflammation markers of blood remained at a high level for a longer period compared with HLA-B27-negative patients. CONCLUSIONS: This is the first population-based study on the epidemiology of juvenile arthritis in Estonia in which the new classification criteria defined by the International League of Associations for Rheumatology (ILAR) have been used. In addition to environmental factors, an increase in awareness among family doctors is a probable reason for the rise in incidence during the study period. HLA-B27 might have predictive value as a marker of chronicity of inflammation.

Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Fulminant type 1 diabetes, which is characterised by a markedly acute onset of diabetes and an absence of islet-related autoantibodies, accounts for 20% of type 1 diabetes in Japan. We aimed to clarify the contribution of the HLA subtype to fulminant type 1 diabetes in Japanese. METHODS: We determined the serological subtypes of HLA-A, -DR and -DQ in 115 patients with fulminant type 1 diabetes, 98 patients with typical type 1A diabetes and 190 normal control subjects. RESULTS: The frequency of HLA-DR4, but not DR9, was significantly higher in fulminant type 1 diabetes, while those of HLA-DR1, DR2, DR5 and DR8 were significantly lower than those in controls. In contrast, DR9 but not DR4 was more frequent and DR2 was extremely rare in typical type 1A diabetes. Haplotype analysis revealed that DR4-DQ4 was significantly more frequent, and both DR2-DQ1 and DR8-DQ1 were less frequent in fulminant diabetes. In type 1A diabetes, DR2-DQ1 was extremely rare while DR9-DQ3 was significantly more frequent. In the combination analysis, the homozygotes of DR4-DQ4 in fulminant type 1 diabetes and DR9-DQ3 in typical type 1A diabetes indicated high odds ratios (13.3 and 13.3, respectively). CONCLUSIONS/INTERPRETATION: Our results suggest that class II HLA contributes to the development of fulminant type 1 diabetes. Susceptibility and resistance of the HLA subtype to type 1 diabetes are distinct between fulminant and typical autoimmune type 1 diabetes.

Association between HLA-A/-B antigens and -DRB1 alleles and nasopharyngeal carcinoma in Tunisia.

Using serologic and molecular methods, 45 nasopharyngeal carcinoma (NPC) patients were typed for HLA class I and class II and were compared to 100 unrelated normal Tunisians. Our results showed that the antigen frequency of HLA-B13 and allelic frequencies of DRB1*03, DRB1*15 were significantly higher in the NPC patients than in the control group (15.5 vs. 4; 26.4 vs. 11.5, and 14.4 vs. 6.5%, respectively) probably indicating a positive association with NPC. Moreover, we observed that HLA-A23 was absent in our NPC sample and was present in 18% of normal controls, and HLA-DRB1*11 was less frequent among the patients compared to the controls (5.5 vs. 14%) suggesting a protective effect of this association with NPC.

Compound heterozygosity of HLA-DR4 and DR1 antigens in Asian Indians increases the risk of extra-articular features in rheumatoid arthritis.

The relationship of HLA-DR antigens in rheumatoid arthritis (RA) patients with the presence of rheumatoid factor (RF), extra-articular features, joint erosions, functional status and response to disease modifying anti-rheumatic drugs (DMARDs) was studied. Seventy-four patients with RA were serologically typed for class II antigens. Clinical features were recorded before starting DMARDs and during follow-up to assess response and side-effects. HLA-DR1 and DR4 antigens were present more frequently in patients with RA than in the general population. The presence of DR4 correlated with RF seropositivity (P < 0.001) while DR1 was associated with seronegativity (P < 0.02). Ten of the 11 patients with extra-articular features had DR1 and/or DR4. Patients with both DR4 and DR1 had a significantly higher frequency of extra-articular features compared with those with only one of these (P < 0.01). HLA-DR4 and DR1 had no relation with the presence of subcutaneous nodules, erosive changes, deformities, response to drugs and side-effects of DMARDs.

HLA antigens in Arabs with lichen planus.

We have HLA typed 50 Arab patients with cutaneous lichen planus who were resident in Kuwait and then compared the antigen incidence with 100 normal controls. There were no significant differences in the antigens of the HLA-ABC loci but there was a significant increase in HLA-DR1 (P = 0.0018, RR = 3.68) and HLA-DR10 (P. corr. = 0.00096, RR = 8.27) and a significant decrease in HLA DR5 (P. corr. = 0.0396, RR = 0.18). The relevance of these findings to earlier reports on lichen planus in which HLA-DR1 (but not DR10) is increased is discussed. This is the first report of HLA antigen frequency in Arab patients with lichen planus, and would support the fact that HLA DR1 is universally associated with the disease, although the more significant association appears to be with HLA-DR10.