IgA antibodies from patients with primary IgA nephropathy bind to collagens I, II, and IV. Here we show that this binding is mediated by the collagen-binding site of fibronectin, which occurs in the circulation in complex with IgA. No antibodies binding directly to collagen were identified.The complexes were isolated by affinity chromatography on gelatin-Sepharose and heparin-Sepharose, both with affinity for fibronectin, followed by adsorption to anti-human IgA immobilized on agarose gel. The presence of fibronectin and IgA antibodies in the isolated complexes is shown by enzymelinked immunosorbent assay, gel electrophoresis, and electrophoretic transfer followed by immunostaining. The presence of an IgA-fibronectin complex in serum and the binding of this complex to collagen demonstrate the necessity of removing fibronectin from serum prior to identifying anti-collagen antibodies.

It has recently been shown that patients with IgA nephropathy have circulating IgA antibodies against extracts of human glomerular basement membrane. The present study extends those observations and demonstrates by using ELISA and immunoblotting techniques that patients with IgA nephropathy have circulating IgA antibodies against collagen IV a chains. The antigenicity ofthe a chains could be destroyed by digestion with collagenase, which indicates that the antigenic site(s) is located on the triple helical part of collagen IV. Furthermore, it was shown by inhibition tests that the IgA antibodies are directed against epitopes also present in collagen I and II isolated after pepsin digestion.

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Sera from 305 consecutive patients in a renal biopsy series were analyzed for the presence of anti-entactin antibodies by ELISA. Of these patients, 59% had primary glomerulonephritis, 21% had secondary glomerulonephritis, while 20% had other nephropathies (noninflammatory conditions like amyloidosis, diabetic nephropathy, nephrosclerosis, etc.). Forty-one of these patients (13.4%) were positive for IgG/IgM antibodies against entactin: 60% of them had primary glomerulonephritis, 35% had secondary glomerulonephritis, while the remaining 3 patients had other nephropathies. Fifteen (70%) of the 23 patients with primary glomerulonephritis had proliferative glomerulonephritis (PGN), whereas 13 (87%) of the 15 patients with secondary glomerulonephritis were due to systemic connective tissue diseases (SCTD): 7 due to SLE, 4 due to SLE like SCTD and two due to other SCTD. There was a peak of incidence corresponding to the group aged 18 to 30 years. A majority of these patients (12 of the total 17) had primary glomerulonephritis and were associated with nephrotic or subnephrotic grade proteinuria, poorly or nonresponsive to immunosuppressive treatment and associated, in several cases, with progressive deterioration of renal function. In addition, there was a tendency to another peak in the age group 51 to 60 years. Most of these patients (6 of the total 8) had glomerulonephritis secondary, mainly, to SLE or SLE like SCTD with milder degree of proteinuria and better preserved renal functions. Anti-entactin antibodies were not found in certain glomerulonephritides like IgA nephropathy and those secondary to systemic vasculitides and in control subjects (healthy subjects, and patients with a variety of non-renal disorders including inflammatory diseases).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of colchicine and colchiceine on fast axonal transport in frog sciatic nerves were studied in vitro. Colchiceine inhibited the transport to about the same extent as colchicine. Preincubation at low temperature potentiated the inhibitory effect of either drug. The polymerization of purified brain tubulin was inhibited by colchiceine at 5-10 times higher concentrations than colchicine. The similarity of the effects obtained with colchicine and colchiceine indicates that both drugs arrest axonal transport by interfering with microtubule function. Colchicine and colchiceine did not affect the levels of high energy phosphates (ATP and CrP) in frog nerves indicating that a reduced energy supply was not responsible for the arrested transport.