To analyze O-linked oligosaccharides (O-glycans) in the hinge region of IgAl in IgA nephropathy (IgAN), the reactivity of IgA1 to jacalin, which specifically binds to O-glycans, was investigated. Initially, renal biopsy specimens from 5 patients with IgAN and 3 patients with other renal diseases were investigated in an immunofluorescence study with jacalin, monoclonal antihuman IgAl and IgA2 antibodies. All of the renal biopsy specimens of IgAN and none of other renal diseases were positively stained by both FITC-labeled jacalin and monoclonal anti-IgA1 antibody. The glomerular staining patterns of FITC-jacalin were similar to those of the monoclonal anti-IgA1 antibody. IgA2 was negative in all specimens. Based on the positive reactivity of deposited IgA1 to jacalin, the binding ability of serum IgA1 to jacalin was evaluated by inhibition assay using D-galactose in patients with IgAN (n = 58), other primary glomerulonephritides (PGN) (n = 41), and healthy controls (n = 52). The frequencies of the patients with serum IgA1 having a high affinity for jacalin were significantly greater in IgAN (19/58, 32.8%) compared with the healthy controls (2/52, 3.8%) and other PGN (4/41, 9.8%). These results suggested that the increased reactivity of O-glycan(s) in the IgAl hinge region to jacalin is due to an unusual glycosylation of serum IgA1 in IgAN.

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IgA class anti-IgA antibody was sought by an immunoabsorbent technique in sera from patients with IgA nephropathy (IgA-N, n = 62), other forms of primary glomerulonephritis (PGN, n = 41), seropositive rheumatoid arthritis (RF-positive, n = 18) and normal controls (c, n = 50). IgA-N (31%) and RF-positive (56%) patients showed a significant increase in IgA anti-IgA antibody levels. The subclass of IgA anti-IgA antibody was predominantly IgAl in both IgA-N and RF-positive patients. Size analysis revealed the dimer/monomer ratio to be significantly increased in IgA-N patients compared with that of RF-positive patients (p = 0.03). These results indicate the possible existence of the dimeric form of IgA class anti-IgA antibody in the circulation of IgA-N patients.

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We studied 26 non-dialysed patients with chronic renal failure [creatinine clearance (CCr) 32.6 +/- 12.7 ml/min]. They were divided into three groups according to their CCr and serum intact parathyroid hormone (PTH) and were given 0.5 micrograms/day oral calcitriol (calcitriol group, n = 8), 3 g/day calcium carbonate (CaCO3 group, n = 10), or neither (control uraemic group, n = 8). Serum intact PTH decreased from 154 +/- 75 to 90 +/- 43 pg/ml in the calcitriol group (P < 0.01) and from 162 +/- 97 to 77 +/- 62 pg/ml in the CaCO3 group (P < 0.001). Calcium carbonate was also effective in suppressing serum tartrate-resistant acid phosphatase, alkaline phosphatase and intact osteocalcin levels, while calcitriol did not suppress serum osteocalcin. Secretion of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) by phytohaemagglutinin A (PHA)-activated peripheral blood mononuclear cells (PBMC) was greater in uraemic patients than in age-matched healthy controls (n = 8). Calcitriol was effective in suppressing secretion of both cytokines, while calcium carbonate was capable of suppressing only TNF-alpha secretion. CCr decreased from 37.4 +/- 15.4 to 33.0 +/- 11.8 ml/min (P < 0.05) in the CaCO3 group, while it did not decrease in either the calcitriol group or the control uraemic group during a 6 month period. These results suggest that supplementation with calcitriol is necessary to maintain bone formation and normalize IL-1 beta and TNF-alpha secretion by activated PBMC in uraemic patients.

To examine the hormonal regulation of the ATP-dependent Ca2+ pump in the kidneys, the ATP-dependent Ca2+ uptake by the basolateral membrane vesicles in the renal cortex was measured using radioactive calcium (45Ca2+) in rats with vitamin D deficiency or rats undergoing thyroparathyroidectomy. The Vmax of the Ca2+ pump activity was increased not only by administering calcitriol, but also by normalizing the serum calcium level in vitamin D-deficient rats. PTH suppressed the Ca2+ pump activity in normocalcemic vitamin D-deficient rats. Thyroparathyroidectomy did not affect the Ca2+ pump activity in the kidneys of normal rats. It was concluded that the ATP-dependent Ca2+ pump activity was depressed by secondary hyperparathyroidism in vitamin D-deficient rats.

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