An antibody-mediated bullous skin eruption caused by chronic renal allograft rejection.
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Autoantibodies↗
Biomedical subjects
J Feehally
Publications and source records attributed to J Feehally.
Accelerated hypertriglyceridemia in patients on continuous ambulatory peritoneal dialysis - a preventable abnormality.
Increasing hypertriglyceridemia is a recognised complication of CAPD. To investigate the etiology lipid clearance studies using the intravenous fat tolerance test were performed in control subjects and in uremic patients before and after six months CAPD treatment. Oral carbohydrate intake was restricted and the use of hypertonic dialysate kept to a minimum. Although serum triglycerides were elevated in the uremic patients before CAPD (3.1 +/- 0.3 mMol/L) no further increase occurred during therapy. Oral carbohydrate intake was restricted to 240-250 Gms/24 hrs and hypertonic dialysate to 5.7 +/- 4.1% of the total. There were no significant changes in fractional removal rate of lipid. Therefore further increases in serum triglycerides in CAPD may be prevented by simple dietary manoeuvres.
Adult↗
Recurrent proteinuria in chronic lymphocytic leukemia.
A case of chronic lymphocytic leukemia complicated by the nephrotic syndrome (due to membranoproliferative glomerulonephritis) is reported. There was complete remission of the proteinuria on two occasions in response to treatment of the leukemia. Possible etiological mechanisms are discussed and review of the literature is presented.
Glomerulonephritis↗
Increased incidence of end-stage renal failure secondary to diabetes mellitus in Asian ethnic groups in the United Kingdom.
Diabetic renal disease is more common in patients of Asian ethnic origin than White Caucasians in the United Kingdom. This study determines whether a disparity in the incidence of end-stage renal failure secondary to diabetes mellitus exists between these ethnic groups. The incidence of treated end-stage renal failure was estimated using the person-time at risk incidence rate for patients receiving renal replacement therapy secondary to diabetes mellitus in the county of Leicestershire from 1979 to 1988. The incidence rate of end-stage renal failure expressed for the estimated population of patients with diabetes mellitus in patients of Asian ethnic origin was 486.6 (95% CI, 185.1 to 788.1) cases per million person-years per year, compared to 35.6 (17 to 54.2) in White Caucasians. All patients of Asian ethnic origin developing end-stage renal failure had non-insulin-dependent diabetes. The high incidence of end-stage renal failure secondary to diabetes mellitus in patients of Asian ethnic origin in the UK imparts significant public health implications for resource planning and allocation, and the need to initiate strategies to ameliorate renal disease in this ethnic group.
Asia↗
Visceral glomerular epithelial cell DNA synthesis in experimental and human membranous disease.
BACKGROUND: Membranous nephropathy (MN) is a 'non-proliferative' glomerulonephritis. However, visceral glomerular epithelial cell (vGEC) proliferating cell nuclear antigen staining and increased glomerular histone mRNA in passive Heymann nephritis (PHN), suggest that vGECs may enter the cell cycle and undergo DNA synthesis. We used in situ hybridisation for histone mRNA, an S-phase specific marker, to investigate this possibility and identify the cellular origin of histone mRNA in PHN and MN. METHODS: PHN was induced in 16 Sprague-Dawley rats. There were 8 saline/serum controls. 12 animals were sacrificed on days 5 and 10. Renal biopsies from 10 proteinuric cases with MN and matched controls were studied. RESULTS: Day-5 Heymann animals demonstrated more S-phase cells/glomerulus than controls (0.53 +/- 0.09 vs. 0.195 +/- 0.045; p < 0.01). Glomerular S-phase cells were also increased in patients compared to controls (0.24 +/- 0.07 vs. 0.04 +/- 0.018; p < 0.03). In both experimental and human MN, the peripheral location and morphology of glomerular histone mRNA-positive cells was typical of vGECs. CONCLUSION: The results in PHN indicate that vGECs recently injured with antibody and complement enter into the cell cycle and undergo DNA synthesis. The S-phase vGECs in MN may indicate the persistence of immune injury. Whether or not this process leads to cell replication is open to question.
Adult↗
Iga nephropathy, antineutrophil cytoplasmic antibodies and crescentic glomerulonephritis in a patient with the Hermansky-Pudlak syndrome.
Hermansky-Pudlak syndrome is an uncommon cause of renal dysfunction. Because of the risk of bleeding in this condition, few patients have undergone a renal biopsy. Renal dysfunction has been attributed to the deposition of ceroid pigment in the tubules and interstitial fibrosis. We report a case with renal biopsy findings of ceroid deposition and interstitial fibrosis, but also of mesangial IgA deposition, crescentic glomerulonephritis, and an interstitial lymphocytic infiltrate. Furthermore, perinuclear antineutrophil cytoplasmic antibodies of the IgG subclass were detected in a blood sample. It is well known that ceroid pigment in this syndrome accumulates in monocytes, macrophages and T lymphocytes and it has been suggested that this may affect their function. We suggest that this novel combination of renal changes might be explained on the basis of alterations in immune mechanisms in the Hermansky-Pudlak syndrome.
Adult↗
Structural features of IgA molecules which contribute to IgA nephropathy.
IgA nephropathy (IgAN) is characterised by the mesangial deposition of polymeric IgA1 (pIgA1). pIgA1 production is reduced in the mucosal immune system in IgAN and increased in the marrow; this switch may be secondary to a defect in gammadeltaT cell control of IgA production. However this does not explain the mechanism by which pIgA1 deposits in the mesangium. There is no direct evidence that classical immune complex deposition occurs in IgAN and alternative mechanisms resulting from physicochemical abnormalities of the IgA1 molecule, particular altered glycosylation, have been proposed. IgA1 has a distinctive hinge region which is a site for O-glycosylation. There is reduced terminal galactose on the hinge region O-glycans of circulating IgA1 in IgAN, perhaps due to a defect in B cell beta1,3 galactosyltransferase. A concomitant O-glycan defect in mesangial IgA1 has not yet been proven. Altered hinge O-glycosylation may have substantial impact on the quaternary structure of the IgA1 molecule influencing its capacity to interact with matrix proteins, IgA receptors on mesangial cells and leucocytes, and complement; it may therefore play a key role in the pathogenesis of mesangial deposition of IgA1 and subsequent glomerular injury in IgAN.
Amino Acid Sequence↗
Response to mucosal antigen challenge in IgA nephropathy.
While IgA nephropathy (IgAN) is characterized by the deposition of glomerular IgA, the source of the deposited IgA is not known, with both the mucosal and systemic IgA systems being implicated. In order to investigate mucosal and systemic antibody production to mucosal antigen challenge in IgAN, 9 patients and 11 controls were immunized intranasally with tetanus toxoid (TT). There was no significant difference in the serum or saliva IgG, IgA, IgA1, or IgA2 antibody production to TT. However, in IgAN there was an increase of in vitro IgA anti-TT production in Epstein-Barr virus transformed cultures of peripheral blood lymphocytes taken after mucosal immunization. This increase in traffic of immunocompetent cells between the systemic and mucosal systems could play a role in the link between the mucosa and glomerulus in IgAN. Systemic immunization with TT following mucosal priming did not result in any difference in the antibody response between patients and controls. There was no evidence from this study that mucosal immunization results in an enhanced antibody response in IgAN or that mucosal priming alters the subsequent systemic antibody response.
Administration, Intranasal↗
In vitro immunoglobulin isotype suppression in immunoglobulin A nephropathy.
IgA nephropathy (IgAN) is characterized by mesangial IgA deposition, and up-regulation of the IgA system is frequently described. This study investigated in vitro immunoglobulin isotype production by peripheral blood mononuclear cells from patients with IgAN and controls, without mitogenic stimulation and under the influence of cell cycle inhibitors and cyclosporin A (CyA). In controls, only IgM production was suppressed by cell cycle inhibitors, and no isotype was affected by CyA. This suppressible IgM production may represent antigen-independent 'natural antibody'. In IgAN, IgM, IgA and IgG were all suppressed by cell cycle inhibitors, and CyA suppressed IgA production. This state of altered immune activation in IgAN demonstrates T-cell-independent IgA production, suggesting that it is IgA 'natural antibody'. In conclusion, we suggest that mesangial IgA deposition may not be antigen dependent but due to some non-immune characteristic of the IgA molecule.
Adult↗
A nephrologist on sabbatical leave in the USA. Report of a Medicine-Gilliland Travelling Fellowship.
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Education, Medical, Continuing↗
Increased IgA and decreased IgG production by Epstein-Barr virus transformed B cells in culture in IgA nephropathy.
Despite many studies describing IgA upregulation both in vivo and in vitro in IgA nephropathy (IgAN), the underlying mechanism of increased IgA production is not known. In this study, Epstein-Barr virus was used to transform B cells in vitro in a T-cell-independent manner in order to investigate immunoglobulin production by B cells in IgAN. B cells from patients with IgAN produced more IgA and less IgG in culture than controls. While both IgA subclasses contributed to the increase in IgA production, only IgA1 synthesis was significantly higher than controls. These results of increased IgA production in patients with IgAN, with a concomitant decrease in IgG production, demonstrate hyperactivity of B cells restricted to the IgA isotype in IgAN.
Adolescent↗