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Human immunodeficiency virus (HIV) infection continues to be a leading cause of morbidity and mortality. HIV-infected individuals are now surviving for a relatively longer period and this is because of easy accessibility to antiretroviral therapy these days. As a result, chronic disease-related complications are now being recognized more often. Kidney disease in HIV-infected children can vary from glomerular to tubular-interstitial involvement. We searched the database to identify various kidney diseases seen in HIV-infected children. We describe the epidemiology, pathogenesis, pathology, clinical and laboratory manifestations, management and outcome of commonly seen kidney disease in HIV-infected children. We also provide a brief overview of toxicity of antiretroviral drugs seen in HIV-infected children. Kidney involvement in HIV-infected children may arise because of HIV infection per se, opportunistic infections, immune mediated injury and drug toxicity. HIV-associated nephropathy is perhaps the most common and most severe form of kidney disease. Proteinuria may be a cost-effective screening test in the long-term management of HIV-infected children, however, there are no definite recommendations for the same. Other important renal diseases are HIV immune complex kidney disease, thrombotic microangiopathy, interstitial nephritis and vasculitis.

Objective: To observe the histopathological and ultrastructural features of coronary artery vasculitis in rabbits caused by repeated intravenous injections of bovine serum albumin (BSA), mimicking Kawasaki disease., Materials and Methods: Twenty weanling rabbits were randomly and equally divided into treatment groups for BSA or normal saline (NS), and administered the respective treatment by intravenous injection once every 12 days for two cycles. Six weeks after the first treatment, rabbits underwent coronary angiography and coronary arteries were removed within 1 h. Histopathological examination was performed by light, scanning electron, and transmission electron microscopy., Results: Coronary arteriography revealed that 3 rabbits (3/10) in the BSA group had various levels of dilation and narrowing of the left coronary arteries, while histological examination showed that 10 rabbits (10/10) had infiltration of the coronary arteries by inflammatory cells. Incomplete endothelium, breakage of elastic fiber, and intimal thickening were also observed in 8 rabbits (8/10) from the BSA group. Ultrastructurally, in 3 rabbits (3/10) in the BSA group, leukocyte migration, shedding of endothelial microparticles from the plasma membranes, incomplete endothelium, abscission of endothelial cells, breakage of the internal elastic lamina (IEL), degeneration of smooth muscle cells in the medial membrane, and swollen mitochondria were detected. By contrast, the IEL of the NS control group was continuous and of uniform thickness., Conclusion: This rabbit model of coronary arteritis displayed histopathological and ultrastructural features similar to those of Kawasaki disease in humans. Breakage of the IEL, a key factor in aneurysm formation, was observed in the coronary arteries. Therefore weanling rabbits may serve as an experimental model for immune complex vasculitis involving coronary arteries that mimics Kawasaki disease.

Light-chain deposition disease (LCDD) of the kidney is defined as deposition of monotypic light chains (LC) within glomerular (GBM) and tubular (TBM) basement membranes. The morphologic features of pure renal LCDD have been presented only in case reports or small series. The aim of this study was to perform a comprehensive evaluation of the light (LM), immunofluorescence (IF), and electron microscopic (EM) features of pure renal LCDD in a large series of biopsies. Out of 46 cases assembled, 42 had multiple myeloma, 2 had monoclonal gammopathy of unknown significance, and in 2 patients no lymphoproliferative disease was identified. The most common LM lesion of LCDD, nodular glomerulosclerosis, was present in only 14 (30%) cases. GBM and/or TBM thickening was found in 3 (6%), mild to moderate mesangial matrix increase in 12 (23%), and unremarkable glomeruli and tubules were seen in 15 (32%) cases. Forty-two had IF and 40 (92%) showed characteristic linear LC immunoreactivity (24 kappa, 16 lambda) along GBM and/or TBM. Among 39 cases in which IF and EM was available, 25 (64%) were positive by both. Two (6%) were negative by IF, but had deposits by EM. In 12 (30%) with immunoreactivity to LC (4 kappa, 8 lambda), no deposits were identified ultrastructurally. This study shows heterogeneous LM lesions in pure LCDD cases. LM alone may be suspicious but not diagnostic of LCDD. Immunofluorescence is more sensitive than EM for detection of LC for the definitive diagnosis of LCDD. This study supports the importance of utilizing kappa and lambda stains in the routine IF panel for diagnosis of LCDD.

There are few data on morphology of light-chain deposition disease (LCDD) of kidney with coexistent light-chain cast nephropathy (LCCN). Here, the authors report the morphology in 23 cases of LCDD and LCCN. They retrospectively evaluated 23 renal biopsies with light (LM), immunofluorescence (IF), and electron microscopy (EM). Twenty-one patients had myeloma, 1 had a monoclonal gammopathy, and in 1 no illness was found. Nodular glomerulosclerosis, the LM lesion suggestive of LCDD, was noted in only 3 of 23 cases. Glomeruli were unremarkable in 16 (69%) cases. The diagnostic casts of LCCN were seen in all biopsies. Linear light chain (LC) immunoreactivity was observed in 23 (100%) cases (18 kappa, 5 lambda); GBM + TBM in 13, TBM only in 7, GBM only in 1, TBM and interstitium in 1, GBM, TBM and mesangium in 1. Casts were positive with same LC in all cases (100%). Fifteen cases (65%) showed granular electron-dense deposits; GBM only in 5, TBM only in 5, GBM and TBM in 4, mesangium in 1. In 8 patients without EM deposits, the diagnosis of LCDD was rendered by IF. Fifteen (65%) had deposits detectable by IF and EM, 8 (37%) had deposits with IF only. LCCN dominated the LM findings in all patients. There were minimal or no glomerular changes by LM. This study shows the lack of characteristic LM findings of LCDD in combined cases of LCDD and LCCN and emphasizes the difficulty for-definitive diagnosis-without IF and EM.

Antiglomerular basement membrane (GBM) disease is characteristically described with linear deposition of IgG along GBM. However, the concurrent glomerular immune complex deposition was not rare and might be contributed to the development of anti-GBM disease. In the current series, glomerular immune complexes were identified in 10 of 47 patients who presented with renal-biopsy-proven anti-GBM disease. Six of the 10 patients complicated with a well-documented glomerulonephritis, including two patients with membranous nephropathy, one patient with IgA nephropathy, one patient with membranoproliferative glomerulonephritis, one patient with Schonlein-Henoch nephritis, and one patient with hepatitis B virus associated membranous nephritis. The other four patients had immune complexes with IgG or IgM predominance deposited in glomerular mesangium without a well-documented glomerulonephritis. Clinical and pathological data of patients with immune complex deposition (n = 10) were compared with those of patients with anti-GBM disease alone (n = 37). There was no significant difference in age, gender, clinical and pathological manifestations, and renal outcome between the two groups. In general, the association of glomerular immune complexes did not lead to a benign prognosis. Plasma exchange and extensive immunosuppressive therapy should be carried out as soon as possible. The immune complexes deposited in glomeruli might participate in the initiation of anti-GBM disease.

Skeletal muscle biopsy and autopsy samples of 132 SLE patients were studied by immunofluorescence and light microscopic techniques. Immune deposits were compared to histologic abnormalities and clinical and serologic findings. Immune deposits with a mainly granular pattern were observed at different locations in 49 patients (37%). They correlated significantly (p<0.001) with inflammatory myopathy, demonstrated in 33(25%), with noninflammatory myopathy which occurred in 38 (29%) vasculitis, observed in 13(10%), and with noninflammatory vasculopathy which was noted in 10 patients (8%). The correlation of muscle immune deposits with anti-DNA antibodies was significant at p= 0.016. Anti-Sm and anti-U1 RNP antibodies were associated significantly with the intensity of immune deposits. Furthermore, a correlation of immune deposits with increased creatine phosphokinase and myopathic electromyogram, but not with evidence of clinical involvement, was shown. A key pathogenetic role of immune deposits in the development of skeletal muscle histologic abnormalities in SLE was demonstrated.

Electron microscopy (EM) is a valuable tool in diagnostic medicine, and in some cases, can be enhanced by immunological methods. A major medical application of EM, diagnostic virology, can frequently be augmented by employment of immunological reagents. Three immunoelectron microscopy (IEM) methods, aggregation, coating, and gold labeling, provide means for serotyping viruses; aggregation by antibody can also be used to concentrate viruses in dilute suspension or to serotype them. As a research tool, IEM can be useful in studying the relationship of various pathogen proteins to the infected cells or tissues. Delineating the subcellular location of viral components can yield information about how virions are constructed, and hence, suggest methods and compounds for inhibiting that process. Conversely, labeling virus-infected cells with antibodies against various cell receptors and proteins can yield information about the association of the proteins with budding virions. Another research example is the identification by immunological staining of virus-infected cells for subsequent ultrastructural identification of the specific cell type involved. Electron microscopy and immunolabeling methods are also useful in the diagnosis of immune complex disorders, including various forms of postinfectious immune complex glomerulonephritis. Precise analysis of immune complex deposits can be accomplished by using EM to pinpoint their location and immunohistology to probe their composition. Finally, a variety of optical microscopic techniques, including some involving immunofluorescent labeling, can be used to identify areas of interest in inhomogeneous tissues for further study by EM.

Experimental colitis was induced in rats by topical irritation of the colonic mucosa with 1 ml of 1% formalin followed by intravenous injection of 0.5 ml soluble immune complexes (IC) made in vitro in antigen excess and having characterized precipitation and complement activation profiles. The rats had been preimmunized with Escherichia coli O14:K7:H- to produce antibodies cross-reactive with colonic mucosa, thus aggravating the colitis to chronicity. Histologic evaluation of inflammation in the colon was performed on days 6, 12, and 18 by determining the number of phagocytic cells. The colitis was inhibited by sulphasalazine therapy given daily, 125.5 mumols (50 mg)/kg body weight, starting on the day when the inflammation was produced with IC and formalin. Sulphasalazine therapy significantly (p less than 0.05) decreased the number of phagocytic cells in the mucosa on days 12 and 18 but not on day 6. The results may give a clue to the beneficial pharmacologic effects of sulphasalazine in the treatment of ulcerative colitis.

The effect of immune complex deposition in intestine was studied in a mercuric chloride-induced experimental autoimmune disease model in the Brown Norway rat. Whereas deposition of autoantibodies in a linear pattern along the basement membrane did not lead to any functional changes, presence of immune complexes along the intestinal basement membrane, occurring after week 35 of the experiment, was associated with intestinal protein loss.

The arteriolar changes in renal biopsy samples were studied by light and electron microscopy and immunohistologic observations. Arteriolar hyaline thickening was found to occur in virtually all renal diseases, regardless of whether these were accompanied by hypertension or not. Only amyloidosis and dense deposit glomerulonephritis were accompanied by specific ultrastructural arteriolar changes. The nonspecific "hyalin" was shown ultrastructurally to contain various components: accumulated basement membrane material, fine granular deposit (with filamentous or lipid details), and granulovesicular and threadlike membrane structures. Presumably the material constituting these structures originates partly from the blood and partly from elements of the vascular wall itself.

A case of asynchronous renal carcinoma with a 15-year course is described. Right nephrectomy and left heminephrectomy were performed. Solitary metastases to pancreas and striated muscle were treated with total pancreatectomy and local excision, respectively. The patient died of renal failure due to progressive immune complex glomerulonephritis, which was documented histologically as well as by clinical observations of intensifying excretion of urinary protein with decreasing selectivity. The glomerular lesion is suggested to have been caused by deposition of tumour-related immune complexes arising from an immune response by the host to his tumour.

A guinea pig pulmonary immune complex disease was used to evaluate local antigen (ovalbumin)-specific lymphoproliferative responses in lung tissue, bronchoalveolar spaces, and hilar lymph nodes (HLN) at various time intervals after challenge. The responses of lung tissue and bronchoalveolar lymphocytes appear to be mediated by T cells, whereas the response of HLN lymphocytes was mediated by B and/or T cells, depending on the stage of the disease. The blastogenic response of HLN lymphocytes to concanavalin A was much greater than that observed in lung tissue or bronchoalveolar lymphocyte preparations, even after the removal of adherent cells, suggesting a possible inherent difference between these cell populations in their response to mitogen. This study demonstrates that lung tissue, bronchoalveolar, and HLN lymphocytes are not only capable of responding blastogenically to specific antigen, but that this responsiveness varies throughout the course of the disease. The lymphoproliferative responses and concurrent changes in the proportion of pulmonary immune effector cells are discussed in relation to cellular immunoregulation during the in vivo progression of this pulmonary immune complex disease.

Changes in immunologic effector cell populations in lung tissue, bronchoalveolar spaces, tracheobronchial lymph nodes, spleen, and peripheral blood were evaluated during the course of a pulmonary immune complex disease in guinea pigs. The number of macrophages, lymphocytes, and neutrophils present in each cell population were determined. T and B lymphocytes were identified by E and EAC rosette formation, respectively. An increase in the total number of lymphocytes in tracheobronchial lymph nodes and a greater proportion of B cells in these lymphocyte populations were observed at 12 and 24 hr postchallenge. The total number of macrophages, lymphocytes, and neutrophils recovered from the bronchoalveolar spaces also increased, as did the proportion of lymphocytes and neutrophils. A similar proportional increase of lymphocytes obtained from lung tissue also occurred. The proportion of B cells in the lymphocyte populations of the bronchoalveolar spaces and lung tissue increased to a maximum at 24-48 hr postchallenge. Cell populations from peripheral blood or spleen remained stable, by all parameters examined, during the disease process. Thus, there appears to be a localization of the immune inflammatory response in the lungs during the course of this pulmonary immune complex disease. In addition, this study provides evidence that immune effector cells obtained by bronchial lavage accurately reflect the cellular changes associated with the acute inflammatory response in lung tissue and pulmonary lymph nodes.