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Biomedical subjects

R M McIntosh

Publications and source records attributed to R M McIntosh.

At least 19 recordsLinked to original sources

Simultaneous immunologic studies of skin and kidney in systemic lupus erythematosus clinicopathologic correlations.

Thirty-two biopsies of kidneys and of normal skin were performed simultaneously on patients with systemic lupus erythematosus (SLE) to determine whether the deposition of immune reactants in skin was correlated with the severity of renal injury or with several serologic measures of systemic disease activity. Immunofluorescent deposits at the dermal-epidermal junction (lupus band test) did not correlate with any clinical or histologic measures of glomerulonephritis or with serologic abnormalities. Immune deposits in dermal venules were found in 56% of the skin biopsies and were correlated with hypocomplementemia and higher levels of immune complexes in serum, and possibly with glomerular subendothelial electron dense deposits. Azathioprine therapy was correlated with absence of both sub-epidermal and vascular immune deposits. Immuno-fluorescent findings on serial skin biopsies on 13 patients were highly inconsistent. It is concluded that the lupus band test is clinically useful only as a diagnostic aid but not helpful in assessing renal or serologic activity of lupus, and that dermal vascular deposits of immunoglobulin or complement are more frequent than previoulsy recognized and correlate with measures of circulating immune complexes.

Adolescent

Acute poststreptococcal glomerulonephritis in Maracaibo. II: Studies on the incidence, nature, and significance of circulating anti-immunoglobulins.

Antiglobulins were measured in the sera of 82 patients with acute poststreptococcal glomerulonephritis and correlated with C1q binding activity, serum levels of immunoglobulins and C3, site of infection, antibody titres to streptococcal enzymes, and the duration of the nephritis and interval from infection. Raised serum antiglobulins were found in 89.2% of the patients. In addition, raised titres were detected at any time during the course of the disease and very early after streptococcal infection. The finding of antiglobulins soon after the infection suggests the possibility that they appear as a primary event in the disease.

Acute Disease

Immune deposit nephritis and single-component cryoglobulinemia associated with chronic lymphocytic leukemia. Evidence for a role of circulating IgG-anti-IgG immune complexes in the pathogenesis of the renal lesion.

2 patients developed the nephrotic syndrome several years after diagnoses of chronic lymphocytic leukemia. In both cases light microscopy showed membranoproliferative glomerulonephritis. Electron microscopy and immunofluorescent staining revealed electron-dense deposits and deposition of immunoglobulins and C3. Both patients had single-component IgG cryoglobulinemia. The eluted glomerular-bound protein contained IgG only. IgG in patients' sera, cryoglobulins, and kidney eluate had kappa light chains only. Immune complexes were detected in the sera and in the cryoglobulins by the Clq binding test. Immunoadsorption studies revealed anti-IgG antibodies in the patients' sera, cryoglobulin, and kidney eluate. Direct immunofluorescent studies using the patients' sera, cryoglobulins, and kidney eluate on frozen sections of patients' kidneys were positive, providing additional evidence for the immune complex nature of the glomerulonephritis. The immunohistochemical studies of our patients are suggestive of the presence of circulating IgG-anti-IgG immune complexes and their possible involvement in the pathogenesis of the glomerulonephritis and the nephrotic syndrome in these 2 cases.

Antigen-Antibody Complex

Etiologic variability of nephropathy in juvenile diabetes mellitus.

Clinicopathologic studies of four patients with juvenile diabetes mellitus and renal disease demonstrated the pathogenetic variability of nephropathy in diabetic patients. Only in one patient was the clinical nephropathy associated with the typical diabetic glomerulosclerosis. Another patient had steroid responsive nephrotic syndrome superimposed on minimal diabetic glomerulosclerosis. A third patient had steroid resistant nephrotic syndrome associated with mild diabetic glomerulosclerosis and with later appearance of Grave's disease. The fourth patient, in addition to moderate diabetic glomerulosclerosis had prominent tubulointerstitial nephritis, the latter probably being responsible for the rapidly declining renal function. The poor prognosis associated with diabetic nephropathy warrants a careful search for other potentially treatable causes of nephropathy in patients with juvenile diabetes mellitus.

Adolescent

Small vessel vasculitis caused by hepatitis B virus immune complexes. Small vessel vasculitis and HBsAG.

In a comprehensive study of 80 patients with vasculitis, 4 had concurrent hepatitis B virus (HBV) infection. Polyarteritis nodosa was present in 2 and in the other 2, cutaneous vasculitis, presenting clinically as palpable or Henoch-Schönlein purpura. In one of these patients skin biopsies demonstrated granular deposits of IgM, C3, C4, and the hepatitis B surface antigen (HBsAg) and electron-dense deposits of aggregated 20-nm particles resembling HBsAg in postcapillary venules. Evidence for circulating HBsAg-immune complexes included increased serum Clq binding activity, decreased serum complement, and a cryoprecipitate containing both HBsAg and IgM anti-HBs. Aggregated 20-nm particles resembling intact HBsAg were also seen by negative staining electron microscopy of the serum cryoprecipitate. This patient fulfills all the criteria for a specific immune complex vasculitis caused by his immune response to a chronic HBV infection. These findings emphasize that HBV infection may be associated with small vessel vasculitis as well as polyarteritis nodosa, mixed cryoglobulinemia, and glomerulonephritis. A similar immune response to other viral infections may be expressed as palpable (Henoch-Schönlein) purpura also.

Adult

Evidence of an autologous immune complex pathogenic mechanism in acute poststreptococcal glomerulonephritis.

Clinical and experimental studies have suggested a role for antiimmunoglobulins in the pathogenesis of glomerulonephritis associated with streptococcal infection. We attempted to localize anti-IgG in the kidneys of 22 patients who had renal biopsies performed 7 to 66 days after the onset of acute poststreptococcal glomerulonephritis (APSGN). In addition to routine localization of immunoglobulins and C3, specimens were stained with neuraminidase-treated, heat-aggregated, and unmodified IgG. Twelve biopsies showed staining with fluorescein-labeled human neuraminidase-treated IgG. A lesser number gave positive staining with the other IgG preparations. Following treatment of slides with 0.01 M citrate buffer, seven previously negative biopsies showed positive staining with neuraminidase-treated IgG. The demonstration of anti-IgG by these methods was possible in 19 out of 22 biopsies. It correlated best with the presence of C3 and IgG, and to a lesser extent with IgM, in the renal glomerulus. These results and our previous finding of elevated levels of serum anti-IgG early in the course of APSGN, and as early as 8 days following the antecedent streptococcal infection, support a role for anti-IgG in the immune pathogenesis of APSGN. Although our series of studies support the hypothesis that anti-IgG is formed to an IgG modified enzymatically by streptococcal product, the formation of this autoantibody to IgG incorporated in an exogenous (streptococcal antigen-antibody) complex can not be ruled out.

Adolescent

Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia.

Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis.

Adult

Severe steroid-responsive nephrosis associated with hypersensitivity.

Sensitivity to cow's whole milk investigated in six patients with the idiopathic nephrotic and an elemental diet was given. After proteinuria had decreased to less than or equal to 500 mg/24 hours on consecutive days patients were challenged with cow's milk. This resulted in the return of significant proteinuria, oedema, and decreased urine volume together with a decrease in serum-IgG concentrations in four patients. Acute alteration of plasma C3 complement component accompanied milk challenge in all 6 patients. There were no consistent alterations in other immunoglobulin concentrations. Intradermal skin testing with cow's milk extract was positive in all patients. These results suggest that in some individuals clinical and biochemical manifestations of the nephrotic syndrome of childhood may be related to hypersensitivity of food products.

Adolescent

Glomerular deposition of renal tubular epithelial antigen in patients with systemic lupus erythematosus: its possible role in lupus nephritis.

Fifty-three renal specimens from 48 patients with SLE were examined for the presence of RTE in the glomeruli. Glomerular RTE, presumably in immune complex form was detected in 60% of the tissues. The deposition of these complexes was related to the severity of histologic changes and activity of SLE. In addition, glomerular localization of RTE was associated with decreased renal function and increased proteinuria. The association between the presence of glomerular RTE antigen, the severity of renal histologic changes and the decreased renal function suggested a possible role for this antigen in the pathogenesis of lupus nephritis.

Adolescent

Experimental autologous immune deposit nephritis in rats associated with mercuric chloride administration.

Serial administration of mercuric chloride to rats was followed by development of antibodies to tubular basement membrane and renal tubular epithelial antigen (RTE) and glomerulonephritis characterized by granular deposits of hosts IgG, C3 and RTE along the glomerular capillary walls. The glomerular fixed antibody was directed against RTE. These studies suggest that tubular injury by mercury may lead to release of RTE and autosensitization and subsequent antibody production to this antigen result in formation of and glomerular deposition of circulating immunopathogenic complexes (RTE-anti-RTE) and glomerular morphologic alterations.

Animals

Autologous immune complex nephritis associated with sickle cell trait: diagnosis of the haemoglobinopathy after renal structural and immunological studies.

A renal tubular epithelial antigen (RTE)--anti-RTE autologous immune complex nephritis associated with sickle cell anaemia (SS) has been reported, but immune complex nephritis has never been described in patients with sickle cell trait (SA). During investigation of a child with "asymptomatic proteinuria" cryoprecipitable complexes of RTE-anti-RTE were detected in the serum and granular deposits of RTE, immunoglobulins, and complement localised on the glomerular basement membranes. Morphological and ultrastructural studies showed increased mesangial matrix, sickled red blood cells in the glomeruli and vessels, and tubular and interstitial abnormalities. These findings prompted haemoglobin electrophoretic studies, which showed previously undiagnosed haemoglobin SA in this patient and her family. These observations suggest that nephritis mediated by similar immunopathogenic mechanisms may be associated with SS and SA haemoglobinopathy. Under some conditions patients with sickle cell trait may experience haemodynamic and oxygenation abnormalities, which may be aetiological factors in the immune complex nephritis associated with SS disease.

Adolescent

The effect of renal hydrodynamics on immune complex deposition.

The role of renal hydrodynamics on renal deposition of immune complexes was evaluated in acute serum sickness. Using i.v. radiolabelled antigen in rabbits under a variety of hydrodynamic alterations, these studies suggested that although intrarenal hydrodynamics influence renal deposition of immune complexes factors other than intrarenal hydrostatic pressure may be important.

Animals