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B Rodriguez-Iturbe

Publications and source records attributed to B Rodriguez-Iturbe.

11 recordsLinked to original sources
PubMed1994

A role for histones and ubiquitin in lupus nephritis?

Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but the pathogenesis is still poorly understood. Experimental evidence now suggests that histones can participate in immune complex formation in lupus nephritis. In a retrospective study, using samples from Northern and Southern Europe, Japan and South America, we searched for glomerular deposits of histones, both in native and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and 70 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining was revealed with rabbit antibodies to synthetic peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of the cases of SLE respectively. In total positive staining with at least one of the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal biopsies revealed positive staining with the above antibodies. None of the biopsy specimens from SLE patients were positive for ss- or ds-DNA, when tested with intercalating dyes. Serum samples were available from 15/48 SLE cases and were analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal regions of core histones and in the C-terminus of histone H1 were often recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched octapeptide of U-H2A. These results support the notion that the nuclear autoantigens histone and ubiquitin may be involved in the induction of glomerulonephritis in human SLE.

Animals↗
PubMed1984

Cell populations and membrane attack complex in glomeruli of patients with post-streptococcal glomerulonephritis: identification using monoclonal antibodies by indirect immunofluorescence.

Poststreptococcal glomerulonephritis (PSGN) had been thought to arise from renal deposition of immune complexes and as such is analogous to acute serum sickness. Recent studies of acute serum sickness in animals and PSGN in humans, however, have suggested a pathogenetic role for cellular immunity. To enlarge on these observations, cellular components of glomeruli were characterized by indirect immunofluorescence in 11 tissues from individuals with PSGN using monoclonal antibodies. These studies demonstrate infiltration of glomeruli by monocytes, granulocytes, and lymphoid cells. Focal accumulations of T lymphocytes were also observed adjacent to Bowman's capsule. Analysis of glomerular T-cell subpopulations revealed a predominance of cells reactive with OKT4 early and with OKT8 later in the course of disease. Proliferation of parietal and visceral epithelial cells was associated with increased binding of BA-1 and J5, respectively. The presence of the membrane attack complex of complement was demonstrated by glomerular reactivity with a monoclonal antibody (poly-C9 MA) which recognizes a neoantigen present in poly-C9. Fluorescence was present along the glomerular basement membrane early and within the mesangium late in the course of disease, a distribution similar to that observed for C3 and C5. These observations suggest that immune cells as well as terminal components of complement either provoke or mark tissue injury in PSGN.

Adolescent↗
PubMed1981

Skin window immune response to normal human IgG in patients with rheumatoid arthritis and acute poststreptococcal glomerulonephritis.

The skin window technic was utilized to determine the reactivity of patients with rheumatoid arthritis (RA) and acute poststreptococcal glomerulonephritis (APSGN) to human IgG (H-IgG). The response to H-IgG was compared in nine patients with RA, 20 patients with APSGN, and 10 normal individuals. All subjects were tested concomitantly with the saline solution used as solvent for H-IgG. The normal controls and five patients were challenged, in addition, with diphtheria-tetanus-pertussis antigen (DPT) to which they had previous prophylactic exposure. The following results were obtained: 1) Four patients with RA and nine patients with APSGN responded with increased lymphocyte migration (more than 2 SD above the normal mean level) at nine and 12 hours. 2) The mean estimated immunogenic lymphocytosis (calculated subtracting the lymphocyte counts of the saline skin windows) of both patient groups was significantly higher than that of controls at the same time intervals. 3) The response of normal individuals and patients to DPT was comparable in time of appearance and intensity to the response of patients to H-IgG. Our studies that patients with RA and APSGN respond to H-IgG in a manner comparable to that observed with a known antigenic stimulus and support a clinical role for antiglobulin reactivity.

Adolescent↗
PubMed1979

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↗
PubMed1976

Epidemic glomerulonephritis in Maracaibo. Evidence for progression to chronicity.

In 1968 an outbreak of 348 cases of acute poststreptococcal glomerulonephritis (AGN) was observed in Maracaibo, Venezuela. During the year, the epidemic had three peaks of incidence. Districts with better sanitation showed a lower incidence of disease than those with less adequate facilities. Endemic cases occur every year. Lowering of serum complement activity was observed in 96% and hypertension in 90% of the patients. The mortality rate in the acute phase during the epidemic was 1.31%. A history of antecedent infection was found in 39% of the cases. 70% of these infections were in the upper respiratory tract. During 1973-74, 120 of the patients (19 adults and 101 children) were reexamined. All but one had been completely asymptomatic. Sixteen patients (13.3%) had one or more of the following abnormalities (group A): low CCr, microscopic hematuria, proteinuria of 1 g/day or more and hypertension. One hundred and four patients (86.7%) were normal by all clinical and laboratory parameters tested (group B). The incidence of persisting disease, as judged by biochemical findings, was significantly higher (P less than .01) in adults (36.7%) than in children (8.9%). Percutaneous renal biopsies from 7 patients of group A, and 8 patients from group B, were studied by light microscopy and immune histology. All biopsies from group A patients had evidence of advanced glomerular disease by light microscopy and by immune histology. Seven biopsies from group B patients were also abnormal showing mild changes with corresponding immunologic findings. Only in one patient was the biopsy completely normal. Our studies indicate that significant numbers of patients progress towards chronicity after epidemic, poststreptococcal AGN. Such progression is more common in adults than in children.

Adolescent↗