HLA-Associated Hemorrhagic Fever with Renal Syndrome Disease Progression in Slovenian Patients

ABSTRACTMajor histocompatibility complex (MHC) class I and class II genes regulate the balance between appropriate aggressive responses and invading pathogens while minimizing the destruction of host tissue. Several studies have shown that in hemorrhagic fever with renal syndrome (HFRS) patients, the disease outcome is determined by a complex interaction between the virus and immunopathologic and human genetic factors. In Slovenia, the severity of the disease caused by Puumala virus (PUUV) is significantly lower than that of HFRS due to Dobrava virus (DOBV). We have determined 23 different HLA-B and 12 different HLA-DRB1 types in Slovenian HFRS patients. Comparison of HLA frequencies between healthy individuals and HFRS patients showed no strong association with the susceptibility for hantaviral infection. Significant associations were recognized when the patient group was separated according to the virus responsible for the infection. DOBV-infected patients have a significantly higher frequency of HLA-B*35 than PUUV-infected patients. For HLA class II genes, the biggest difference between the PUUV- and DOBV-infected groups of patients was in HLA-DRB1*13, where this phenotype was more frequent in PUUV-infected patients, especially in the severe form of the disease. HLA-B*07 could play a protective role in PUUV-caused HFRS in the Slovenian population. Our study shows diverse associations of HLA molecules with DOBV- and PUUV-induced HFRS, and therefore, we presume that different hantaviruses are presented differently through the same HLA molecules and that this might lead to either a more severe or a milder form of the disease. In line with this idea, we have noticed that HLA-B*35 might be a genetic risk factor for DOBV infection in the Slovenian population.

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Lupus anticoagulants: strong association with the major histocompatibility complex class II and platelet antibodies

British Journal of Haematology ◽

10.1046/j.1365-2141.1997.2103027.x ◽

1997 ◽

Vol 98 (2) ◽

pp. 342-345 ◽

Cited By ~ 16

Author(s):

Simon Panzer ◽

Ingrid Pabinger ◽

Michael Eduard Gschwandtner ◽

Wolfgang Richard Mayr ◽

Daniela Hütter

Keyword(s):

Major Histocompatibility Complex ◽

Major Histocompatibility Complex Class ◽

Strong Association ◽

Class Ii ◽

Complex Class ◽

Major Histocompatibility ◽

Lupus Anticoagulants ◽

Platelet Antibodies ◽

Histocompatibility Complex

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Features of hematological changes in patients with hemorrhagic fever with renal syndrome depending on the severity and period of the disease

Aspirantskiy Vestnik Povolzhiya ◽

10.17816/2072-2354.2019.19.3.72-80 ◽

2020 ◽

Vol 19 (5-6) ◽

pp. 72-80

Author(s):

Anna V. Lyubushkina

Keyword(s):

Initial Period ◽

Hemorrhagic Fever ◽

Severe Form ◽

Urea Level ◽

Reactive Protein ◽

Comparison Groups ◽

Depth Study ◽

Group 2 ◽

Severity Of The Disease ◽

Hematological Changes

This article provides a comparative analysis of the features of hematological changes in patients with hemorrhagic fever with renal syndrome (HFRS) in the Samara region, depending on the severity and period of the disease. In-depth study of the metabolic profile was carried out in patients with early hospitalization (until the 5th day of illness). Enzyme studies (ALT, AST, LDH, CPK), indicators of the protein spectrum and electrolytes were performed in patients (n = 73) who were admitted in the initial period of the disease. The patients with proven cases of HFRS were divided into 3 comparison groups: group 1 (n = 22) represents cases of a mild form of the disease (urea level up to 8.3 mmol / l, creatinine up to 130 mmol / l); group 2 (n = 25) includes the cases of a moderate form of the disease (urea level up to 19 mmol / l, creatinine up to 300 mol / l,); group 3 (n = 26) comprises cases of a severe form of the disease (urea level above 19 mmol / l, creatinine above 300 mol / l). The comparison of the groups was performed by using single-factor analysis of variance, between-group comparisons was carried out by means of Dunnetts test. Spearmans correlation analysis was performed to investigate the relationships. Our study demostrates that thrombocytopenia and lymphopenia, as well as a significant increase in ferritin and C-reactive protein (1020-fold) are the early signs of any severity of the disease. Both the level of urea and creatinine and their concentration in the blood as well as aggravated trombo- and lymphocytopenia, determine the severity of the disease. The revealed differences in the key metabolic indicators on the 3rd5th day of the disease will allow to solve the problem of early prediction of the severity of the disease, which will be fully manifested in the oliguric period.

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Regulation of major histocompatibility complex class II gene expression

Microbes and Infection ◽

10.1016/s1286-4579(99)80524-3 ◽

1999 ◽

Vol 1 (11) ◽

pp. 833

Author(s):

W Reith

Keyword(s):

Gene Expression ◽

Major Histocompatibility Complex ◽

Major Histocompatibility Complex Class ◽

Class Ii ◽

Complex Class ◽

Major Histocompatibility ◽

Histocompatibility Complex

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Relationship of Major Histocompatibility Complex Class II Genes to Inhibitor Antibody Formation in Hemophilia A

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647359 ◽

1990 ◽

Vol 64 (04) ◽

pp. 564-568 ◽

Cited By ~ 22

Author(s):

Lloyd E Lippert ◽

Lyman Mc A Fisher ◽

Lawrence B Schook

Keyword(s):

Major Histocompatibility Complex ◽

Factor Viii ◽

Antibody Formation ◽

Rflp Analysis ◽

Class Ii ◽

Major Histocompatibility ◽

Odds Ratios ◽

Inhibitory Antibody ◽

Histocompatibility Complex ◽

Hla Dr

SummaryApproximately 14% of transfused hemophiliacs develop an anti-factor VIII inhibitory antibody which specifically neutralizes factor VIII procoagulant activity. In this study an association of the major histocompatibility complex (MHC) with inhibitor antibody formation was evaluated by restriction fragment length polymorphism (RFLP) analysis using BamHI, EcoRI, HindII, PstI, PvuII and TaqI digested genomic DNA probed with DP beta, DQ alpha, DQ beta and DR beta class II MHC gene probes. The RFLP patterns for 16 non-inhibitor and 11 inhibitor hemophiliac patients were analyzed. These 24 enzyme:probe combinations generated 231 fragments. Fifteen (15) fragments associated with the inhibitor phenotype; odds ratios ranged from 5.1 to 45 and lower bounds of 95% confidence intervals were > 1.000 for all 15 fragments. Five (5) fragments associated with non-inhibitors, with odds ratios ranging from 6.4 to 51.7. This report establishes a MHC related genetic basis for the inhibitor phenotype. No statistically significant differences in the distribution of serologically defined HLA-DR phenotypes were observed between the inhibitor and non-inhibitor groups.

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