Biomedical subjects
Publications and source records attributed to F C Berthoux.
All patients are excreting the virus in urines and in 4 cases in stools. The virus has also been isolated from the blood. These cases focused on the possible role of enteroviruses as causal agents for the glomerulonephritis.
Two HLA identical brothers with mesangial IgA glomerulonephritis are reported. Patient 1 developed gross hematuria at age 12 and required chronic hemodialysis at age 20. Patient 2 presented at age 21 with gross hematuria and normal renal function, the follow up period is only 9 months. Neither of these patients had nerve deafness, ocular defects or complement abnormalities. The family history did not support a diagnosis of classical hereditary nephritis, but a genetic linkage is strongly suggested by the identical HLA phenotypes of these brothers (A10 - A32 - B13 - B35). The B35 antigen has previously been suspected to be linked to this disease. These observations strongly support the hypothesis of an aberrant, genetically controlled, immune response, in patients with mesangial IgA glomerulonephritis.
Familial cases of mesangial IgA glomerulonephritis (MGN) have raised the possibility of a genetic control in this disease. In 50 patients with MGN, diagnosed on renal biopsy, and in 105 controls, we have compared the distribution of HLA antigens (A and B loci). We found a significant increase in the frequency of HLA Bw35 antigen in the patient group compared with controls (36% versus 13%: p less than 0.02). There was no significant difference between the Bw35 positive and negative MGN subgroups, in clinical, serological, and pathological data. Both subgroups had elevated mean serum IgA levels (154% of normal), and also mean serum IgM levels (146%). However, the follow-up data exhibited a significantly worse prognosis (p less than 0.01) in the Bw35 positive subgroup: 9 out of 18 patients versus 4 out of 32 progressed to chronic renal failure (serum creatinine greater than 1.5 mg/dl). We have established a genetic linkage between the HLA complex and the occurrence of MGN. The Bw35 antigen may serve as a marker (risk of disease = 4), in particular for poor prognosis cases.
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The association between glomerulonephritis and hereditary C2 complement deficiency has been found in 4 out of 8 children of a family. The hemolytic complement (CH50) was much decreased in homozygot subjects and slightly decreased in heterozygot. C1q, C4, C3, C5, C1s INA were normal, the C2 was found at an intermediate or null rate; CH50 could be reconstitued by purified human C2. The C2 deficiency genes were associated with HLA A10 B18 (father) and HLA A29 B18 (mother) haplotypes but HLA D allels were different on the 2 haplotypes. The C2 deficiency appears to lead to an increased susceptibility to immune-complexe diseases, specially to glomerulonephritis.
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The drug, pentosan-poly-sulfoester (PPS), has an anticomplementary activity (ACA) on human serum both in vitro and in vivo, as judged by a reduction in total hemolytic complement activity (CH 50). In vitro, this ACA is very potent, immediate and temperature independent. In vivo this ACA obtained with a IV dose of 100 mg per 8 hours eg 300 mg/24 h, increases with the duration of treatment (mean time:30 days), suggesting a cumulative effect. Eleven patients with glomerulonephritis (GN) received such a treatment (8 with acute post-streptococcal GN and 3 with mesangio-proliferative GN). In patients with already marked hypocomplementemia, the ACA is difficult to establish, while in patients with normal complement activity or moderate hypocomplementemia, the decrease of CH 50 level in serum is obvious. There was no significant change inthe serum level of C3, C4, properdin factor B as measured by radial immunodiffusion technique. The clinical course of these GN was apparently not affected by this treatment. Neverthless, the in vivo ACA of PPS is firmly established and we can speculate that this functional depletion in complement may prevent or decrease the liberation of humoral mediators of inflammation.
In vitro, the drug pentosan-poly-sulfoester (PPS) changes the electrophoretic migration of different proteins from the complement and properdin systems, such as native C3 (beta 1C globulin), C3c (beta-1A globulin), C3d (alpha-2D globulin), C1s inactivator (ClsINA), Clq and properdin factor B (B). Their more anodal migration is the consequence of a molecular alteration and persists after prolonged dialysis. These structural changes, yet undefined, explain the loss of functional activity of these proteins, and the anticomplementary activity of this drug. Moreover, PPS is able to block the alternate pathway activation by its action on properdin factor B (C3 proactivator). In fact, in presence of PPS, the activators of the properdin systems such as C3 nephritic factor are inactive. These altered mobilities are also responsible for the overestimation in the antigenic concentration of B (+ 45%), C4 (+27%) and C3/C3c (+ 14%), found in human serum containing 50 mg/ml of PPS. PPS has an original action upon the complement and properdin systems, which allows its clinical use as a potent inhibitor of the humoral mediators of inflammation.
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Various aspects of immunity in cystic fibrosis were studied in 24 children and compared with the results in 13 children with other types of chronic bronchial infection. The complement was not significantly altered: number of lymphocytes, delayed hypersensitivity skin reactions, number of T (an B) cells, phytohaemagglutinin lymphocyte stimulation were virtually normal. Only the phagocytic activities (chemotaxis, phagocytosis, bacteridal activity) were altered in 20 out of 24 patients with cystic fibrosis and in a comparable percentage of patients with other types of chronic bronchial infection. No serum inhibitory factor was found and leukocyte enzyme activities were normal. This deficiency of phagocytic functions seems to be, at least in part, secondary to infection.
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The clinical association between glomerulonephrtis (GN) and malignant hematological disease is very rare. We report, in a 24 years old male, the occurrence of an apparently idiopathic nephrotic syndrome with minimal change glomerular lesions. This GN was in fact closely related to the progression of a stage 2A of Hodgkin's disease, following an infectious mononucleosis contracted one year ago. The nephrotic syndrome responded well to the therapy by Prednisone and Chlorambucil, and the complete remission persisted after eradication of Hodgkin's disease and despite early treatment discontinuation. Renal vein thrombosis, renal amyloidosis and renal interstitial infiltration with malignant cells were ruled out. Immunofluorescent and electron microscopy examination of the renal biopsies were consistent with, but not demonstrative of, an immune complex nephritis. Because of the chronological succession of infectious mononucleosis, Hodgkin's disease, and GN, we are stressing the possible oncogenic and immunogenic role of the Epstein-Barr virus.
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