Uromodulin in Rheumatoid Arthritis

Uromodulin, also known as Tamm-Horsfall protein, is a protein abundantly excreted in the urine in healthy individuals. It is synthesized in the thick ascending limb of Henle (TALH) and the early distal convoluted tubule. Its biologic function is still obscure; however, some experimental studies indicated that it might serve as an important urinary defense factor against bacterial colonization and stone formation.

There are controversial publications on the frequencies of urinary tract infections and nephrolithiasis in patients with mutations of uromodulin gene. Deposition of mutated uromodulin in the urinary system may lead to tubular cell dysfunction and apoptosis. These alterations may subsequently cause tubular atrophy and interstitial fibrosis . Moreover, the release of abnormal uromodulin after apoptosis through basolateral secretion may elicit an immune response which may give rise to an immune-mediated tubulointerstitial nephritis .

Uromodulin can activate the other components of the immune system and may modulate the inflammatory and immune responses through different mechanisms .

Experimental studies yielded that uromodulin negative mice displayed splenomegaly with infiltration of white pulp by macrophages and increased levels of TNF-α and interleukin-1 . Rheumatoid arthritis is a systemic autoimmune condition that may eventually result in the joint damage, disability and premature mortality.

Inclusion criteria

• Patients who diagnosed of rheumatoid arthritis as criteria of ACR/EULAR 2010.
• All patients age range is 18-80 years.

Exclusion criteria

• Renal failure
• Hepatic insufficiency
• Diabetes mellitus
• Other collagen vascular diseases,
• History of smoking and consumption of alcohol