Cystatin A and HIV-1 p24 antigen expression in tonsillar lymphoid follicles during HIV-1 infection and during highly active antiretroviral therapy.
Cystatin A is a natural cysteine proteinase inhibitor and is found in a wide variety of normal cells. The physiologic role of Cystatin A is not fully known, however. Cystatin A is present in large amounts in follicular dendritic cells, which are important in HIV-1 pathogenesis. We analyzed Cystatin A expression in tonsillar sections from 20 patients at various stages of HIV-1 infection. There was a significant (P < 0.001) difference in Cystatin A fractions between patients and controls, with medians (ranges) of 0.61 (0.46-0.83) and 0.86 (0.78-0.90), respectively. Inverse correlations (Spearman rho) existed between Cystatin A and the rate of follicular fragmentation (rho = -0.658) and HIV-1 p24 antigen expression (rho = -0.622) in germinal centers and the amount of HIV-1 RNA in tonsillar tissue (rho = -0.765). The Cystatin A fraction declined from early chronic HIV-1 infection and was significantly lower in patients with a CD4 count below as compared with above 300 cells/muL of blood (P < 0.001), suggesting a favorable initiation of highly active antiretroviral therapy (HAART) at this level. Regeneration of Cystatin A to normal levels was shown in 11 patients 12 and 48 weeks after initiation of HAART, whereas the rate of follicular fragmentation was still elevated. Thus, we found Cystatin A to be a sensitive marker during HIV-1 infection and for regeneration of follicular lymphoid tissue during HAART.
Centre for Research in Virology, Gade Institute, Bio-Building, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. pal.voltersvik@gades.uib.no
Pål
P
Voltersvik
Leif
L
Bostad
Anne Margarita
AM
Dyrhol-Riise
Geir Egil
GE
Eide
Bård Ingvald
BI
Røsok
Jan
J
Olofsson
Birgitta
B
Asjö
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015891:Cystatins / Q000032:analysis* / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000737:chemistry / Q000473:pathology / Q000821:virology; D016655:HIV Core Protein p24 / Q000032:analysis*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D019562:Viral Load
D015891:Cystatins; D016655:HIV Core Protein p24; D012367:RNA, Viral