Mlycop/c~s~afermenfans (lncognitus Strain) Infection in the Kidneys of Patients With Acquired lmmunodeficiency Syndrome and Associated Nephropathy: A Light Microscopic, Immunohistochemical, and Ultrastructural Study FRANK A. BAUER, MD, CPT, USA DOUGLAS J, WEAR, MD, COL, USA PETIER ANGRIll, MD, COL, USA AND SHYH-CHING LO, MD, PHD We studield renal tissues from 203 patients with acquired immunodeficiency syndrome (AIDS). Of the 203 patients, 20 showed light-microscopic changes characteristic of AIDS-associated nephropathy (AAN). Fifteen of the 20 (group A) were examined by immunohistochemistry using Myco#zsmafermentans (incognitus strain)-specific monoclonal antibodies and electron microscopy. Renal tissues from all 15 AAN patients showed positive staining for the incognitus strain mycoplasmal antigens within glomerular endothkelial and epithelial cells, glomerular basement membrane, tubular epithelial cells and casts, and mononuclear interstitial cells. Ultrastructural study of these 15 cases revealed mycoplasma-like structures in various locations including glomerular epithelial and endothelial cells, glomerular basement membrane, tubular epithelial cells and casts, and mononuclear interstitial. cells. In a parallel study, renal tissues from 15 patients with AIDS with essentially normal renal histology or mild interstitial mononuclear cell infiltration (group B) were also examined. These tissues showed no evidence of incognitus strain mycoplasmal infection in renal parenchymal cells; however, occasional scattered mononuclear interstitial cells were positive for the antigens of this organism. Renal tissues from five patients dying with non-AIDS diseases (group C) showed no staining for the incognitus strain antigens in any location. Therefore, infection of renal parenchymal cells by M fermentam (incognitus strain) in the kidneys of AIDS patients is apparently associated with AAN. HUM PATHOL 22:63-69. Copyright ii‘) 1991 by W.B. Saunders ‘Company
and pathologic manifestations of the A 1DS-associated nephropathv (AAN). Although pathologic descriptions of AA;1 have varied slightly, the major morphologic characteristics that have emerged are: (1) focal segmental and global glomerulosclerosis, frequently characterized by visceral epithelial cell hypertrophy and vacuolization; (2) microcystic dilatation of tubules which contain large proteinaceous casts: (3) tubular cell degeneration or necrosis; and (4) variable degrees of interstitial edema and inflammation. I-’ The major ultrastructural finding in AAK is the presence of Aumerous tubuloreticular inclusions within glomerular endothelial cells.“-’ ’ These structures are apparently induced by increased interferon levels lvhich occur in patients wrth AIDS as well as other diseases such as systemic lupus erythematosus. Several theories have been proposed to explain the nephropathy, including glomerular hyperfiltration (hypertension), postglomerular capillarv obstruction,’ mesangial injury, and circulating soluble toxins (cvtokines) which damage glomerular and tubular ecithelial cells. More recently, direct infection of renal epithelium by human immunodeficiency virus (HIV) has been proposed.‘” Because the nephropathy may be the initial manifestation of AIDS. preceding more advanced stages of the syndrome bv 3 to 20 months or more, the term HIV-associated ‘nephropathy is preferred by many workers. i.x.“i Recently, the isolation and identification of a pre\.iouslv unrecognized pathogen called lbirus-like infectious ‘agent (VLIA) were described. I-l.] ’ Subsequently, studies (1) demonstrated the pathogenic nature of this organism in experimental monkeys’“; (2) characterized VLIA as a novel pathogenic mycoplasma tentatively termed A4ymplusnza irwgnitus. which was shown to be closely related to a rarel) isolated human mycoplasma. lFf~copla.sn~ci frrmfWans’7; (3) demonstrated the presence of ‘Z’I~&O$US in necrotizing lesions of multiple organs from six non-AIDS patients who died of an acute flu-like illnesslH: and (4) demonstrated apparent systemic infection and the presence of this same infectious microorganism in multiple organs from 22 of 32 patients dying with AIDS.“’ In the later two reports, imrnunohrstologic, in situ hybridization, and electron microscopic techniques were used to identify this organism in thymus.
The renal complications of patients with acquirecl ilnmunodef‘iciency syndrome (AIDS) have been recognized since 1984. Numerous studies from that time to the present have described the clinical
From the American Kegistr) ot Patho&) and Drpartment of Intectious and Parasitic Disease Pathology. Armed Forces Institute of Pathologv, LVashington. DC; and the Department 01 Patholog). Walter Ke,:d Arms Medic-al (Zenter. U’ashington. DC:. Accepted fol publicatioli April k3. 1990. Kg u~o~cL\:mvcopiasma. virus-like infectious agent, acquired acquired immunodef’i~ienc~ SVI~Immtunodeticietl~~ syndrome. tlronlr-associat~tl tlephropath\. The opinions ot. assertions contained herein d1.c the private \ iews ot tht- author\ and are not to be construed ns official ot- a\ t-eflecting the VHSVSof thy Department ot the Army or the Department of Detenre. Address correspondence and reprint requests to Shyh-CAing Lo. MD. F’hD. Department of Infectious and Parasitic- Disease Pathology. Arme~l Force-‘; Institute of Pathology, Washington. I)
and pathologic manifestations of the A 1DS-associated nephropathv (AAN). Although pathologic descriptions of AA;1 have varied slightly, the major morphologic characteristics that have emerged are: (1) focal segmental and global glomerulosclerosis, frequently characterized by visceral epithelial cell hypertrophy and vacuolization; (2) microcystic dilatation of tubules which contain large proteinaceous casts: (3) tubular cell degeneration or necrosis; and (4) variable degrees of interstitial edema and inflammation. I-’ The major ultrastructural finding in AAK is the presence of Aumerous tubuloreticular inclusions within glomerular endothelial cells.“-’ ’ These structures are apparently induced by increased interferon levels lvhich occur in patients wrth AIDS as well as other diseases such as systemic lupus erythematosus. Several theories have been proposed to explain the nephropathy, including glomerular hyperfiltration (hypertension), postglomerular capillarv obstruction,’ mesangial injury, and circulating soluble toxins (cvtokines) which damage glomerular and tubular ecithelial cells. More recently, direct infection of renal epithelium by human immunodeficiency virus (HIV) has been proposed.‘” Because the nephropathy may be the initial manifestation of AIDS. preceding more advanced stages of the syndrome bv 3 to 20 months or more, the term HIV-associated ‘nephropathy is preferred by many workers. i.x.“i Recently, the isolation and identification of a pre\.iouslv unrecognized pathogen called lbirus-like infectious ‘agent (VLIA) were described. I-l.] ’ Subsequently, studies (1) demonstrated the pathogenic nature of this organism in experimental monkeys’“; (2) characterized VLIA as a novel pathogenic mycoplasma tentatively termed A4ymplusnza irwgnitus. which was shown to be closely related to a rarel) isolated human mycoplasma. lFf~copla.sn~ci frrmfWans’7; (3) demonstrated the presence of ‘Z’I~&O$US in necrotizing lesions of multiple organs from six non-AIDS patients who died of an acute flu-like illnesslH: and (4) demonstrated apparent systemic infection and the presence of this same infectious microorganism in multiple organs from 22 of 32 patients dying with AIDS.“’ In the later two reports, imrnunohrstologic, in situ hybridization, and electron microscopic techniques were used to identify this organism in thymus.
The renal complications of patients with acquirecl ilnmunodef‘iciency syndrome (AIDS) have been recognized since 1984. Numerous studies from that time to the present have described the clinical
From the American Kegistr) ot Patho&) and Drpartment of Intectious and Parasitic Disease Pathology. Armed Forces Institute of Pathologv, LVashington. DC; and the Department 01 Patholog). Walter Ke,:d Arms Medic-al (Zenter. U’ashington. DC:. Accepted fol publicatioli April k3. 1990. Kg u~o~cL\:mvcopiasma. virus-like infectious agent, acquired acquired immunodef’i~ienc~ SVI~Immtunodeticietl~~ syndrome. tlronlr-associat~tl tlephropath\. The opinions ot. assertions contained herein d1.c the private \ iews ot tht- author\ and are not to be construed ns official ot- a\ t-eflecting the VHSVSof thy Department ot the Army or the Department of Detenre. Address correspondence and reprint requests to Shyh-CAing Lo. MD. F’hD. Department of Infectious and Parasitic- Disease Pathology. Arme~l Force-‘; Institute of Pathology, Washington. I)
