In IgA Nephropathy [IgAN], unknown agents cause the glomeruli to become — and to stay — inflamed. IgAN is the world’s most common glomerulonephritis [inflammation of the glomeruli], but its pathogenesis [how the disease develops] is not known. IgAN is considered to be an immune-complex mediated disorder (or immunologically mediated disorder), which means that immune complexes may not be the direct cause of the disease but they help bring about the end result, which is widespread inflammation of the kidneys.
Immune complexes form when the body is exposed to an antigen, such as a virus, bacteria, toxin, or even allergen. In response, your body sends out antibodies, which are immunoglobulins produced by a certain class of white blood cells known as B-cells. There are five main classes of these immunoglobulins, with IgA [immunoglobulin A] being the main one directed against bacterial and viral antigens.
Antibodies lock onto the surfaces of viruses and other foreign cells, producing antigen-antibody aggregates known as immune complexes that your body targets and attacks. Normally, these immune complexes circulate through the bloodstream until being removed by the liver and other organs. In IgAN, however, they become trapped in the glomeruli.
Once trapped, immune complexes become like magnets for the rest of the body’s immune response. Macrophages and other cells race to the area to release enzymes and generate toxic oxygen radicals that kill bacteria and viruses but also injure local tissues. Trapped immune complexes can also stimulate the overproduction of extracellular matrix, a substance which, surrounds and supports tissue cells. Inflammatory chemicals released during the immune response increase the permeability of the glomerular capillary walls, causing blood being filtered in the kidneys to leak protein and fibrinogen. Fibrinogen, crucial to the process by which blood clots, develops into “crescents,” which form scar tissue that obstructs circulation through the glomerulus. Eventually, deprived of blood, the tubules and glomerulus die, thus destroying the nephron and forcing other nephrons to take up its work.
What happens in IgAN is essentially a vicious cycle
Inflammatory chemicals increase the permeability of the glomerular capillary wall, and that increased porosity enhances the absorption of other chemicals that stimulate cellular growth and, ultimately, structural damage. These changes take time because our kidneys have a lot of excess capacity built into them. The damage is, however, slowly progressive and, in the case of sclerosis [scarring], irreversible.
We do not know what antigen triggers IgAN, nor do we know whether IgAN results from defects in the body’s creation or elimination of immune complexes. There is evidence that immunoglobulin A is overproduced in the bone marrow of IgAN patients; some patients also show decreased capacity to remove immune complexes from their systems.
Because so many IgAN patients have a cold or gastrointestinal illness shortly before the onset of symptoms in the kidneys, it is likely that IgAN starts with an immune response to infectious agents. Perhaps protracted exposure to antigens — as in a recurrent viral illness, or the multiple illnesses experienced by some IgAN patients — sends the immune system into overdrive. The blood of IgAN patients often shows high concentrations of IgA antibodies to a type of protein found in many bacteria, as well as antibodies to many viruses. Certain viruses, once established in the body as a low-level chronic infection, could serve as a continuing source of antigen for the formation of additional IgA immune complexes — and for the perpetuation of injury to the kidneys. It is quite common for IgAN to present after an individual has had an illness such as strep throat, ear infection, etc., that was treated with antibiotics. Antibiotics are effective against bacteria but not against viruses and can even suppress the immune system as far as viral infections are concerned, perhaps allowing a viral infection to become chronic.
Viruses can also over-sensitize the immune system, inducing autoimmune reactions in which the body becomes allergic to itself. Few IgAN patients, however, show a positive anti-nuclear antibody test [ANA], which is an important tool in diagnosing such autoimmune diseases as systemic lupus erythematosus.
It’s clear that IgAN is not simply a kidney disease but rather an immunological disorder that affects the kidneys, as diabetes is an immunological disorder that affects the pancreas. It may also be a disease, like diabetes, that affects the micro blood vessels. If true, this would explain some common extra-renal symptoms, such as headaches, temporary vision problems, and difficulties concentrating.
About Us
The IgA Nephropathy Foundation’s mission is to be a patient-centric organization focused on finding a cure for IgA Nephropathy. Using the power of the patient community we are focused on funding research, using patient advocacy to empower our patients, and building a network of support. As a patient run organization, we will work together with the hope of finding better treatment options and the ultimate cure. By patients, for patients.