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Sökning: id:"swepub:oai:DiVA.org:kth-309278" > Serine Protease HTR...

Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy

Al-Rabadi, Laith Farah (författare)
Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
Caza, Tiffany (författare)
Arkana Labs, Little Rock, AR USA.
Trivin-Avillach, Claire (författare)
Boston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.
visa fler...
Rodan, Aylin R. (författare)
Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.;Univ Utah Hlth, Mol Med Program, Salt Lake City, UT USA.;Univ Utah Hlth, Dept Human Genet, Salt Lake City, UT USA.;Vet Affairs Salt Lake City Hlth Care Syst, Med Serv, Salt Lake City, UT USA.
Andeen, Nicole (författare)
Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA.
Hayashi, Norifumi (författare)
Boston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.;Kanazawa Med Univ, Kanazawa, Ishikawa, Japan.
Williams, Brandi (författare)
Univ Utah Hlth, Moran Eye Ctr, Salt Lake City, UT USA.
Revelo, Monica P. (författare)
Univ Utah Hlth, Dept Pathol, Salt Lake City, UT USA.
Clayton, Fred (författare)
Univ Utah Hlth, Dept Pathol, Salt Lake City, UT USA.
Abraham, Jo (författare)
Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
Lin, Edwin (författare)
Univ Utah Hlth, Dept Human Genet, Salt Lake City, UT USA.
Liou, Willisa (författare)
Univ Utah Hlth, Dept Pathol, Salt Lake City, UT USA.
Zou, Chang-Jiang (författare)
Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
Ramkumar, Nirupama (författare)
Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
Cummins, Tim (författare)
Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA.
Wilkey, Daniel W. (författare)
Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA.
Kawalit, Issa (författare)
Int Renal Care Assoc, Amman, Jordan.
Herzog, Christian (författare)
Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA.
Storey, Aaron (författare)
Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA.
Edmondson, Rick (författare)
Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA.
Sjöberg, Ronald (författare)
KTH,Affinitets-proteomik
Yang, Tianxin (författare)
Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.;Vet Affairs Salt Lake City Hlth Care Syst, Med Serv, Salt Lake City, UT USA.
Chien, Jeremy (författare)
Univ Calif Davis Hlth, Dept Biochem & Mol Med, Davis, CA USA.
Merchant, Michael (författare)
Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA.
Arthur, John (författare)
Univ Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA.
Klein, Jon (författare)
Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA.;Robley Rex Vet Adm Med Ctr, Louisville, KY USA.
Larsen, Chris (författare)
Arkana Labs, Little Rock, AR USA.
Beck, Laurence H. (författare)
Boston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.
visa färre...
Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA Arkana Labs, Little Rock, AR USA. (creator_code:org_t)
American Society of Nephrology (ASN), 2021
2021
Engelska.
Ingår i: Journal of the American Society of Nephrology. - : American Society of Nephrology (ASN). - 1046-6673 .- 1533-3450. ; 32:7, s. 1666-1681
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background Identification of target antigens PLA2R, THSD7A, NELL1, or Semaphorin-3B can explain the majority of cases of primary membranous nephropathy (MN). However, target antigens remain unidentified in 15%-20% of patients. Methods A multipronged approach, using traditional and modern technologies, converged on a novel target antigen, and capitalized on the temporal variation in autoantibody titer for biomarker discovery. Immunoblotting of human glomerular proteins followed by differential immunoprecipitation and mass spectrometric analysis was complemented by laser-capture microdissection followed by mass spectrometry, elution of immune complexes from renal biopsy specimen tissue, and autoimmune profiling on a protein fragment microarray. Results These approaches identified serine protease HTRA1 as a novel podocyte antigen in a subset of patients with primary MN. Sera from two patients reacted by immunoblotting with a 51-kD protein within glomerular extract and with recombinant human HTRA1, under reducing and nonreducing conditions. Longitudinal serum samples from these patients seemed to correlate with clinical disease activity. As in PLA2R- and THSD7A- associated MN, anti-HTRA1 antibodies were predominantly IgG4, suggesting a primary etiology. Analysis of sera collected during active disease versus remission on protein fragment microarrays detected significantly higher titers of anti-HTRA1 antibody in active disease. HTRA1 was specifically detected within immune deposits of HTRA1-associated MN in 14 patients identified among three cohorts. Screening of 118 "quadruple-negative" (PLA2R-, THSD7A-, NELL1-, EXT2-negative) patients in a large repository of MN biopsy specimens revealed a prevalence of 4.2%. Conclusions Conventional and more modern techniques converged to identify serine protease HTRA1 as a target antigen in MN.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

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