23. Antibodies to Tamm-Horsfall Urinary Glycoprotein in Patients with Urinary Tract Infection, Reflux Nephropathy, Urinary Obstruction and Paraplegia

Lynn, Kelvin L.; Bailey, Ross R.; Groufsky, A; Hunt, John S.; Bean, Allan R.; McGiven, A. R.

doi:10.1159/000409258

Cited by 15 publications

(12 citation statements)

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“…Increased production of THP-specific autoantibodies is a consistent finding in several inflammatory disorders and infections of the urinary tract (13,29,30). Furthermore, THP has previously been shown to be a powerful autoantigen when rats, mice, or rabbits were challenged with autologous THP (31)(32)(33).…”

Section: Thp Induces Phenotypic Maturation Of Human Monocyte-derived mentioning

confidence: 79%

“…Furthermore, cytotoxic T cells with specificity for THP and anti-THP Abs were present in affected animals. Ab responses to THP are a well-known phenomenon in patients with infections of the urinary tract such as interstitial cystitis (37,38) and acute pyelonephritis (30,39,40), where THP has been discussed to be involved in kidney scarring leading to overt renal insufficiency (29,41). Moreover, elevated autoantibody levels against THP could be involved in chronic pyelonephritis and subsequent renal damage (15,16).…”

Section: Discussionmentioning

confidence: 99%

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Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4–dependent mechanism

Säemann¹,

Weichhart²,

Zeyda³

et al. 2005

J. Clin. Invest.

202

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Tamm-Horsfall glycoprotein (THP) is expressed exclusively in the kidney and constitutes the most abundant protein in mammalian urine. A critical role for THP in antibacterial host defense and inflammatory disorders of the urogenital tract has been suggested. We demonstrate that THP activates myeloid DCs via Toll-like receptor-4 (TLR4) to acquire a fully mature DC phenotype. THP triggers typical TLR signaling, culminating in activation of NF-κB. Bone marrow-derived macrophages from TLR4-and MyD88-deficient mice were nonresponsive to THP in contrast to those from TLR2-and TLR9-deficient mice. In vivo THP-driven TNF-α production was evident in WT but not in Tlr4 -/-mice. Importantly, generation of THP-specific Abs consistently detectable in urinary tract inflammation was completely blunted in Tlr4 -/-mice. These data show that THP is a regulatory factor of innate and adaptive immunity and therefore could have significant impact on host immunity in the urinary tract.

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Section: Thp Induces Phenotypic Maturation Of Human Monocyte-derived mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4–dependent mechanism

Säemann¹,

Weichhart²,

Zeyda³

et al. 2005

J. Clin. Invest.

202

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“…They were also higher than values observed in the test with the native molecule (18). Higher values of antibodies to Tamm-Horsfall protein in patients with vesicoureteral reflux have already been reported (15,16). Higher values of antibodies to Tamm-Horsfall protein in patients with vesicoureteral reflux have already been reported (15,16).…”

Section: Discussionmentioning

confidence: 57%

“…in the part of the kidney most frequently damaged by pyelonephritis, many authors (3)(4)(5)(6)(7)(8) have proposed that" Tamm-Horsfall protein could be involved in the pathogenesis of pyelonephritis and therefore useful in its diagnosis. The role of antibodies to Tamm-Horsfall protein in the diagnosis of acute pyelonephritis (10)(11)(12)(13) and in detection of vesicoureteral reflux (14)(15)(16) is still controversial. Its physiological role remains unclear (9).…”

Section: Introductionmentioning

confidence: 99%

Short Communication

1996

CCLM

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The aim of this study was to determine antibodies to Tamm-Horsfall protein subunits in patients with acute pyelonephritis. The protein subunits used in this determination were prepared by chemical treatment of Tamm-Horsfall protein isolated from the urine of healthy individuals. Values for IgG and IgA were significantly higher (p < 0.05 and p < 0.01 respectively) in patients than in healthy persons, while IgM class antibodies were significantly higher only in the test performed with subunits obtained with 8.3 mol/1 acetic acid (THP-A) (p < 0.05). Values for all three classes determined in the test with THP-A were significantly higher in patients with vesicoureteral reflux than in patients with normal radiological findings (p < 0.05). Antibodies to Tamm-Horsfall protein subunits isolated from the urine of patients with acute pyelonephritis should also be determined.

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“…Importantly, antibody responses against THP are well known in patients with UTIs, such as in interstitial cystitis [34,35] and acute pyelonephritis [36][37][38][39][40], where THP is thought to be involved in kidney scarring leading to overt renal insufficiency in susceptible individuals [41,42]. Moreover, abnormally elevated autoantibody levels against THP are thought to be involved in the development of chronic pyelonephritis and its associated renal damage [26,43,44].…”

Section: Thp and Inflammatory Disorders Of The Urinary Tractmentioning

confidence: 99%

The multiple functions of Tamm–Horsfall protein in human health and disease: A mystery clears up

Weichhart

Zlabinger

Säemann

2005

Wien Klin Wochenschr

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Tamm-Horsfall protein (THP) is exclusively produced by renal tubular cells of the distal loop of Henle and is the most abundant urinary protein in mammals. The physiological function of THP has remained elusive for over half a century; however, new lines of research position it as a central antimicrobial molecule combating urinary tract infection (UTI). Furthermore, the genetic basis of familial juvenile hyperuricemic nephropathy (FJHN), glomerulocystic kidney disease (GCKD) and autosomal dominant medullary cystic kidney disease 2 (MCKD2) has been recently attributed to mutations within the THP gene. In these clinical conditions misfolded THP accumulates in the tubular cells, ultimately leading to overt renal insufficiency. UTI is the most common nonepidemic bacterial infection in humans, where both innate and adaptive components of the immune system as well as the bladder epithelium are involved in its prevention and clearance. Since the urogenital tract is devoid of typical physical barriers such as mucus or a ciliated epithelium, soluble mediators with potent anti-bacterial capabilities might exist. Recently, genetic ablation of the THP gene was shown to lead to severe infection and lethal pyelonephritis in experimental models of UTI. In addition, mounting evidence indicates that, beyond simply a direct antimicrobial activity, THP is a potent immunoregulatory molecule that induces specific THP-directed cell-mediated immunity. In light of these novel findings the particular role of THP as a specialized defense molecule in the urinary tract is discussed.

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23. Antibodies to Tamm-Horsfall Urinary Glycoprotein in Patients with Urinary Tract Infection, Reflux Nephropathy, Urinary Obstruction and Paraplegia

Cited by 15 publications

References 0 publications

Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4–dependent mechanism

Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4–dependent mechanism

Short Communication

The multiple functions of Tamm–Horsfall protein in human health and disease: A mystery clears up

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