Secondary IgA Nephropathy
Section snippets
Epidemiology of Secondary IgA Nephropathy
Compared with primary IgAN very little is known about the incidence of secondary IgAN. In the series from France reported by Berthoux, pp. 4-9, in this issue IgAN secondary to cirrhosis accounted for 9% of all biopsy-proven cases of IgAN over a 12-year period. Similar to primary IgAN, the apparent prevalence of secondary IgAN will be influenced by renal biopsy practice, for example, in high-risk patients with coagulopathy secondary to hepatic dysfunction. IgAN typically is considered to be a
Pathophysiologic Relationship of Primary and Secondary IgA Nephropathy
The initiating event in the pathogenesis of primary and secondary IgAN is the mesangial deposition of IgA. The recurrence of glomerular IgA deposits in up to 60% of patients with primary IgAN who receive renal allografts indicates that mesangial IgA probably is derived from a circulating pool of pathogenic IgA.18 Not all IgA that deposits in the mesangium triggers a mesangial response characterized by glomerular injury, arguing that mesangial IgA deposition and the development of
Environmental Antigens
Many studies have found increased circulating IgA-IC containing food antigens in IgAN12, 13, 14, 21, 22 and a number of studies have reported changes in various clinical and laboratory parameters on exposure to specific foods.15, 22 Circulating IgA antibodies to a variety of milk and egg proteins including casein and bovine serum albumin have been reported in IgAN15, 23 and indirect immunofluorescence has identified mesangial IgA-IC deposits containing casein, soybean protein, and rice protein.
IgA Synthesis
IgA synthesis requires close cooperation between B and T lymphocytes and precise regulation of the lymphocytic microenvironment. It is therefore not surprising that clonal disorders of predominantly B-lineage cells (lymphoma and IgA myeloma) have been linked on occasion with excessive IgA production and IgAN.6, 32 Interestingly, in the majority of cases high circulating levels of IgA alone are insufficient to cause IgAN, it is only when the monoclonal IgA has specific physicochemical
Clearance of Circulating IgA Containing Immune Complexes
IgA normally is cleared from the circulation by the liver and by leukocytes through receptor-mediated endocytosis. A study in primary IgAN using radiolabelled complexes of IgA and IgG from normal individuals has shown reduced hepatic clearance in IgAN.33 Hepatocytes express an asialoglycoprotein receptor (ASGP-R) that recognizes asialyl N- and O-linked carbohydrate chains on a wide variety of glycoproteins including IgA.34 Hepatic ASGP-R–mediated endocytosis therefore is likely to be an
Hepatic IgAN
Hepatic IgAN occurs most frequently but not exclusively as a complication of alcoholic liver disease. Hepatic IgAN is associated with alterations in the IgA immune system characterized by high levels of circulating IgA-IC.40, 41 It has been proposed that hepatic IgAN is a chance association of 2 common conditions,42 however, most evidence suggests hepatic IgAN is a distinct clinicopathologic entity.43 Information on hepatic IgAN is based largely on autopsy and biopsy studies.42, 44, 45, 46, 47,
Celiac Disease
CD is characterized by malabsorption, chronic mucosal inflammation affecting the small intestine, and villous atrophy. These occur as a direct result of exposure to wheat gluten or related rye and barley proteins. It is associated strongly with HLA-DQ2 and/or DQ8, but there also may be a contributory effect from non-HLA genes.66 CD has been associated with a wide range of diseases and immune disorders including IgAN.67 The presence of high levels of IgA against food antigens including gliadin
IgAN Secondary to Mucocutaneous Infection
As previously discussed, acute and chronic infection with a range of pathogens can be associated with both acute exacerbation and slow progression of primary IgAN. This is seen most commonly with mucosal infection including tonsillitis, pharyngitis, infections of the upper and lower gastrointestinal tract, urinary tract, and respiratory tract. There are also case reports documenting associations with periodontal disease and tooth abscesses. There is currently no evidence in human beings that
Conclusions
Without a clearer understanding of the pathogenesis of primary IgAN it remains difficult to dissect out those diseases in which there is only a chance association with primary IgAN and those diseases in which there might be shared pathophysiology. In our opinion many of the associations in the literature describe environmental and microbial triggers in primary IgAN, which undoubtedly drive the generation of pathogenic IgA and mesangial IgA deposition, but do not induce fundamental changes in
References (78)
- et al.
Adult primary IgA nephropathy and common viral infections
J Infect
(1996) - et al.
Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy
Kidney Int
(2004) - et al.
Pathogenesis of IgA nephropathy
Semin Nephrol
(2004) - et al.
Incidence of latent mesangial IgA deposition in renal allograft donors in Japan
Kidney Int
(2003) Recurrent IgA nephropathy after renal transplantation
Semin Nephrol
(2004)- et al.
Detection of bovine serum albumin in the circulating IgA immune complexes of patients with IgA nephropathy
Clin Immunol Immunopathol
(1987) - et al.
Clearance of polymeric IgA aggregates in humans
Am J Kidney Dis
(1989) - et al.
Cell biology of the asialoglycoprotein receptor system: a model of receptor-mediated endocytosis
Int Rev Cytol
(1985) - et al.
Renal glomerular lesions in unselected patients with cirrhosis undergoing orthotopic liver transplantation
Pathology
(1995) - et al.
Presence and origin of IgA1- and IgA2-containing circulating immune complexes in chronic alcoholic liver diseases with and without glomerulonephritis
Clin Immunol Immunopathol
(1985)
Cirrhotic glomerulonephritis: incidence, morphology, clinical features, and pathogenesis
Am J Kidney Dis
Properties of immunoglobulin A in serum of individuals with liver diseases and in hepatic bile
Gastroenterology
Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics
Gastroenterology
Letter: cirrhotic glomerulonephritis and secretory immunoglobulin A
Lancet
Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac diseaseSIGEP Study Group for Autoimmune Disorders in Celiac Disease
Gastroenterology
Antiendomysial antibodies in Berger’s disease
Am J Kidney Dis
High levels of IgA antigliadin antibodies in patients who have IgA mesangial glomerulonephritis but not coeliac disease
Lancet
Celiac disease and HLA DQ in patients with IgA nephropathy
Am J Gastroenterol
Schistosomiasis and the kidney
Semin Nephrol
IgA nephropathy
J Am Soc Nephrol
Glomerular IgA deposition in liver disease
Nephrol Dial Transplant
Inflammatory bowel disease, ankylosing spondylitis, and IgA nephropathy
J Clin Rheumatol
IgA nephropathy in rheumatoid arthritis
Nephron
IgA nephropathy in systemic lupus erythematosus
Clin Exp Rheumatol
Lymphomas and IgA nephropathy
Nephrol Dial Transplant
Role of chlamydia pneumoniae (TWAR) in IgA nephropathy
Nephron
Circulating IgA, IgG, and IgM class antibody against Haemophilus parainfluenzae antigens in patients with IgA nephropathy
Clin Exp Immunol
IgA-containing immune complexes after challenge with food antigens in patients with IgA nephropathy
Clin Exp Immunol
Antibodies to dietary antigens in IgA nephropathy
Clin Nephrol
Glomerular deposition of food antigens in IgA nephropathy
Clin Exp Immunol
Effects of a gluten-free diet in primary IgA nephropathy
Clin Nephrol
Occurrence of mesangial IgA and IgM deposits in a control necropsy population
J Clin Pathol
The pathogenic role of IgA1 O-linked glycosylation in the pathogenesis of IgA nephropathy
Nephrology (Carlton)
T-cell homing receptor expression in IgA nephropathy
Nephrol Dial Transplant
IgA-associated renal diseases: antibodies to environmental antigens in sera and deposition of immunoglobulins and antigens in glomeruli
J Clin Immunol
Response of circulating immune complexes to food challenge in relapsing IgA nephropathy
Pediatr Nephrol
Low-antigen-content diet in the treatment of patients with IgA nephropathy
Nephrol Dial Transplant
Food sensitivity: the kidney and bladder
Dietary lectins and disease
Cited by (91)
Genomic Study on Blood Culture Isolates From Patients With Staphylococcus Infection-associated Glomerulonephritis
2022, Kidney International ReportsIgA Nephropathy: An Interesting Autoimmune Kidney Disease: IgA Nephropathy
2021, American Journal of the Medical SciencesCitation Excerpt :Many patients with secondary IgAN have mesangial hypercellularity and expansion of the matrix. No specific histologic feature on the renal biopsy differentiates primary from secondary IgAN.98 Chronic liver disease, especially alcoholic cirrhosis, is the leading cause of secondary IgAN,99 and likely arises from glomerular accumulation of IgA1 due to impaired hepatic clearance.98
Secondary IgA Nephropathy Shares the Same Immune Features With Primary IgA Nephropathy
2020, Kidney International Reports