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Histomorfologija in imunohistologija postinfekcijskega glomerulonefritisa v odvisnosti od trajanja bolezni in vrste okužbe
Avtor: Dejan Hermann
Mentor: akad. prof. dr. Dušan Ferluga
Somentor: znan. sod. dr. Alenka Vizjak
IZHODIŠCA: Pri bolnikih z akutnim postinfekcijskim glomerulonefritisom ugotavljajo poleg klasicne histomorfološke slike endokapilamega proliferacijskega in eksudacijskega glomerulonefritisa širok spekter histomorfološkega in imunohistološkega izražanja bolezni, ki je lahko posledica stadija bolezni, individualne odzivnosti in/ali razlik v vrsti okužbe. V dosegljivi literaturi so odnosi med histomorfološkimi spremembami in odlagami imunskih reaktantov opisani pomanjkljivo. Cilj raziskave je zato bil natancneje opredeliti le-te v patogenezi verjetno kljucne odnose v odvisnosti od trajanja bolezni in vrste okužbe.
BOLNIKI IN METODE DELA: Retrospektivna raziskava je vkljucevala 113 ledvicnih biopsij 91 moških in 22 žensk, ki so izpolnjevali klinicne kriterije za diagnozo akutnega postinfekcijskega glomerulonefritisa. Vzorci ledvicnega tkiva so bili obdelani po standardni svetlobno in imunofluorescencno mikroskopski tehnologiji. V skladu z uveljavljeno metodologijo v nefropatologiji smo semikvantitativno ocenili stopnjo mezangijske, endokapilarne in mezangiokapilarne proliferacije, eksudacijske reakcije, tubulo-intersticijskih sprememb in sprememb na žilah ter glomerulnih imunskih odlag. Ekstrakapilarno proliferacijo, globalno in segmentno glomerulosklerozo smo ocenili v odstotkih prizadetih glomerulov. Glede na obliko imunskih odlag smo ugotavljali tri imunofluorescentne vzorce: ogrlicast, vzorec zvezdnatega neba in mezangijski. Za preverjanje razlik in povezanosti rezultatov smo uporabljali statisticne metode: Pearsonov hi-kvadrat test, Kruskal-Wallisow test in Spearmanov test korelacije rangov.
REZULTATI: V 54% primerov je bil kot povzrocitelj okužbe, ki je predhodila pojavu glomerulonefritisa, odkrit streptokok, v 6% stafilokok, v 5% streptokok in stafilokok, v 35% pa povzrocitelj ni bil dokazan. Potrdili smo, da je za prvi mesec poteka bolezni znacilno odlaganje IgG in komponente komplementa C3 z vzorcem zvezdnatega neba v povezavi z glomerulno endokapilamo proliferacijo in eksudacijo (p<0,005). V drugem in tretjem mesecu bolezni je prevladoval vzorec mezangijskega odlaganja C3 (p<0,005), pogosto majhne intenzivnosti, v povezavi z mezangijsko proliferacijo (p=0,07). Le neznacilno sta se v poteku glomerulonefritisa povecala odstotek skleroziranih glomerulov ter obseg žilnih sprememb. Tubulo-intersticijske spremembe smo ugotovili pri vec kot polovici bolnikov v vseh obdobjih poteka, vendar praviloma v majhnem obsegu. Ogrlicast vzorec odlaganja imunskih reaktantov smo ugotovili pri 8 (7%) bolnikih v povezavi z najbolj intenzivno endokapilarno in mezangiokapilarno proliferacijo ter eksudacijo, izkljucno le v prvih dveh mesecih poteka bolezni (p<0,005). Ekstrakapilarne polmesece smo ugotovili pri 27 (24%) bolnikih, vendar le žarišcno in najvec v 38% ledvicnih telesc, skoraj izkljucno v prvih dveh mesecih bolezni (p<0.05). Kot nenavadni so izstopali primeri z endokapilamo proliferacijo (4/14), eksudacijsko reakcijo (5/14) in glomerulnimi kapilarnimi stenskimi imunskimi odlagami z vzorcem zvezdnatega neba (5/14) po vec kot treh mesecih trajanja glomerulonefritisa. Razen tega, intenzivnost vnetnih sprememb v posameznih primerih ni korelirala z vzorcem in intenzivnostjo imunskih odlag.
ZAKLJUCKI: Naša raziskava je potrdila znacilno povezanost med imunofluorescentnim mikroskopskim vzorcem zvezdnatega neba in ogrlicastim vzorcem z glomerulno endokapilarno proliferacijo in eksudacijo v prvem in delno v drugem mesecu poteka akutnega postinfekcijskega glomerulonefritisa. Za kasnejši potek bolezni sta znacilna mezangijski vzorec odlaganja C3 in mezangijska proliferacija. Ekstrakapilarno polmesecasto proliferacijo in tubulointersticijske spremembe ter ireverzibilni globalno in segmentno glomerulosklerozo smo pogosto ugotavljali, vendar te spremembe pri vecini bolnikov zaradi majhne raszežnosti niso neugodno usmerile poteka bolezni. Odstopanja od teh pravil v naši raziskavi so bržcas posledica individualnih razlik v odzivnosti, saj nam ni uspelo dokazati ocitnih razlik glede na vrsto okužbe, ampak le nekoliko pogostejše polmesece in IgA v imunskih odlagah po stafilokokni oz. neopredeljeni okužbi.
[Abstract / English version]
Histomorphology and immunohistology of postinfectious glomerulonephritis in relation to duration of the disease and type of infection
Author: Dejan Hermann
Mentor: akad. prof. dr. Dušan Ferluga
Co-mentor: znan. sod. dr. Alenka Vizjak
AIM: Patients with acute postinfectious glomerulonephritis can express a wide spectrum of histomorphological and immunohistological changes beside the classical picture of endocapillary proliferative and exudative glomerulonephritis which can be a reflection of the stadium of the disease, individual responsivness and/or diferent type of infection. Reports about relations between histomorphological changes and immune deposits are poor. The aim of our study was to evaluate these relations which are probably of main importance in pathogenesis in relation to duration of the disease and type of infection.
PATIENTS AND METHODS: The retrospective study included 113 kidney biopsy from 91 men and 22 women with diagnosed postinfectious glomerulonephritis. Kidney biopsy tissue samples were examined by standard light and immunofluorescent microscopy techniques. Mesangial, endocapillary and mesangiocapillary proliferation, exudation, tubulo-intersticial changes, vascular lesions and glomerular immune deposits were evaluated semiquntitatively in accordance with recognized methodology in nephropatology. Extracapillary proliferation, global and segment glomerulosclerosis were evaluated in percentage of affected glomeruly. According to immune deposits we described three immunofluorescent patterns: garland, starry sky and mesangial. We used Pearsons c2-test, Kruskal-Wallis test and Spearmans test to evaluate differences and correlations of our results.
RESULTS: Streptococcus was confirmed to be causally related to postinfectious glomerulonephritis in 54% of cases. Staphylococcus was found in 6% and both streptococcus and staphylococcus were found in 5% of cases. No causative agent has been demonstrated in 35%. We confirmed that IgG and complement component C3 deposits, revealing a starry sky pattern and significantly associated with glomerular endocapillary proliferation and exudation (p<0.005) were characteristic for the first month of the disease course. In the second and third month of the disease, mesangial pattern of C3 deposition predominate often of mild intensity and associated with a mesangial proliferation (p=0.07). The increase in the percentage of sclerosed glomeruli and intensity of vascular lesions of the course of the disease were statistically nonsignificant. Tubulo-intersticial changes were found independently of the duration of glomerulonephritis in more than half of the patients, but were regularly mild. A garland pattern was observed in 8 (7%) patients accompanied by very intensive endocapillary and mesangiocapillary proliferation and exudation, exclusively in the first two months of the disease (p<0.005). Extracapillary crescents were found in 27 (24%) patients, but only focally and involving a maximum of 38% of glomeruli. They were found almost exclusively in the first two months of the disease (p<0.05). An unusual occurrence of endocapillary proliferation (4/14), exudative reaction (5/14) and glomerular capillary starry sky deposit (5/14) still present after three months of the glomerulonephritis course should be pointed out. In addition, the intensity of infammatory changes in particular cases did not correlate with the pattern and intensity of immune deposits.
CONCLUSIONS: Our study showed significant association of starry sky and garland pattern with endocapillary proliferation and exudation in first and partly in second month of acute postinfectious glomerulonephritis. Mesangial pattern of C3 deposits and mesangial proliferation are significant for the later course of the disease. Extracapillary proliferation, tubulo-interstitial changes, global and segmental glomerulosclerosis were often found but were of little intensity and did not affect the course of the disease in most patients. Aberrations from this conclusions are probably the cause of individual differences in responsiveness, because we didn't manage to prove obvious differences according to type of infection. Only slightly more frequent extracapillary crescents and IgA in immune deposits were found in patients with glomerulonephritis mediated by staphylococcal and nondefined infectious agent, respectively.