During the last two decades, the number of the urinary system pathologies at children [1,2, 10], and obstructive anomalities [2,3] in particular, has increased considerably, calling for more research on their etiopathogenesis, diagnostics and treatment. Despite a great number of studies concerning etiological aspects of inborn obstructive uropathy (IOU) [4,5,6,7], some diagnostic questions of differentiation between IOU and some similarly appearing diseases and conditions, are still poorly studied. Intensity of IOU´s clinical symptoms obviously depends on how strong the primary pathology is complicated with a secondary infection [6,8]. That is why we tried to find out, if there are any immunogenetic markers of obstructive pyelonephritis (OP), and whether it is possible to prognosticate a secondary infection?
We examined 117 Russian children aged between 8 till 15, with a secondary chronic obstructive pyelonephritis and intact kidney function. We studied the distribution of the HLA-complex antigens, their phenotypic and haplotypic combinations. Locuses HLA-A, HLA-B, HLA-C were identified with the help of the two-step micro lymphocytotoxity test (Terasaki P. at al, 1970), locuses HLA-DR and HLA-DQ - via long protocol of polymerase chain reaction using a standard serum set of the Russian Research Institute of Hematology and Transfusiology, St. Petersburg. СD22-lymphocytes for DR-typing and DQ-typing were obtained by filtration of lymphocyte suspension through nylon fiber. In locus HLA-A were determined 15 specificities, in locus HLA-B - 28, in locus HLA-C - 4, in locus HLA-DR - 14 and in locus HLA-DQ - 12 specificities. Antigen frequency rate was determined as a number of persons bearing the antigen compared to the total number of patients in the group . Frequency of phenotypic antigen combinations was determined separately in locuses HLA-A and HLA-B, frequency of haplotypic antigen combinations was determined by formula of Mattiuz P. et al (1970). In order to measure essentiality of discrepancy in antigen distribution in the compared groups, we used a fitting criterion (Χ2) adjusted for variation continuity; using special mathematical tables, fitting criterion Х2 was changed into coefficient of difference reliability (Р). To determine degree of association for different forms of inborn obstructive uropathies with immunogenetic parameters, we used a criterion of relative risk (RR), according to Sweigaard A., Rider L.P. (1994) . Relative risk criterion shows, how often this disease or condition develops in people with a specific HLA-antigen, in comparison with those who do not have it. It is accepted, that when the RR equals or is higher than 2,0, there is a positive association between the marker and the disease (predisposition to disease); and when the RR is smaller than 1,0 - it is a sign of an individual resistance to this pathology. In order to describe this «+» or «-» association quantitatively, we determined the values of etiological fraction (EF) and preventive fraction (PF) correspondingly . Control group in this study included 253 virtually healthy children of the same population sample.
It was revealed, that patients with OP demonstrated a reliable positive association between the disease and inter-locus combination of antigens HLA-A11-B27 in tissues (0,85% compared to 0,01% in control, RR=2,7). We also found the major histocompatibility antigens that prove an individual resistance to this pathology: HLA-DRB1*07 (16% compared to 30,1% in control, Х2 =6,5, Р<0,05, RR= 0,45, PF=0,163); HLA-DRB1*09 (0% compared to 2% in control, Х2 =4,4, Р<0,05, RR=0,21, PF=0); HLA-DRB1*15(2) (22% compared to 36,9% in control, Х2 =6,15, Р<0,05, RR= 0,49, PF=0,186); intra-locus antigen combination HLA-A9-11 (0,85% compared to 7% in control, Х 2 =4,6, Р<0,05, RR=0,25); and also haplotypic combinations HLA-A2-B12 (8,6% compared to 62% in control, RR=0,06); HLA-A3-B7 (7,7% compared to 84,1% in control, RR=0,02); HLA-A11-B35 (2,6% compared to 29,9% in control, RR=0,07).
To sum up, the patients with OP demonstrated a reliable positive associative connection of the disease with inter-locus antigen combination HLA-A11-B17. Carrier state of this immunogenetic marker increases the a risk for the development of the disease by factor of 2,7 (RR=2,7). Resistance to this pathology have individuals with antigens HLA-DRB1*07, HLA-DRB1*09, HLA-DRB1*15(2), phenotype HLA-A9-11 и haplotypic combinations HLA-A2-B12, HLA-A3-B7, HLA-A11-B35.
Specific immunogenetic determinants let use immunogenetic methods, to determine the risk for complications such as secondary infections, after an obstructive pathology, or resistance to it, and thus, to optimize medical tactics for diagnostics and treatment of this pathology at children.
- Karpenko V.S., Khripta F.P., Romanenko A.M. et al. Hydronephrosis. Kiev: Health; 1991. 239.
- Papayan A.V., Savenkova N.D. Clinical nephrology at children: Manual. - St. Petersburg; 1997. 718.
- Greenfield S., Salem Y., Seidel F., Feld L. Child. Nephrol. Urol. 1990; 10: 44-48.
- Illek Y.Y., Zaitseva G.A., Razin M.P. et al. Urology. 2001; 2: 42-45.
- Pugachev A.G., Kudryavtsev Y.V., Larionov I.N., Chumakov А.М. Urology and nephrology. 1996; 3: 3-5.
- Razin M.P., Zaitseva G.A., Illek Y.Y. Urology. 2007; 2: 71 - 76.
- Krueger RP, Ash, Silver MM et al. Ural. Clin. North Am. 1980; 7: 231 - 242.
- Mandell J, Kinard HV, Mittlestoedt CA, Seeds JW. J Urol. 1984; 123: 303.
- Zaretskaya Y.M. Clinical immunogenetics. Moscow: Medicine; 1983. 196.
- Razin A.P., Razin M.P. et al. European Journal of Natural History. 2006; 5: 91-93.
- Sveigaard A., Ryder L.P. Tissue Antigens. 1994; 43: 18 - 27.
The work was submitted to to the International Scientific Conference «HIGHER PROFESSIONAL EDUCATION. MODERN ASPECTS OF THE INTERNATIONAL COOPERATION», Tel Aviv, May 1-7, 2009. Came to the editorial office on 04.04.2009.