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  • Al-Rabadi, Laith FarahUniv Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA. (författare)

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

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • American Society of Nephrology (ASN),2021
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-309278
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-309278URI
  • https://doi.org/10.1681/ASN.2020101395DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20220224
  • 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 och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Caza, TiffanyArkana Labs, Little Rock, AR USA. (författare)
  • Trivin-Avillach, ClaireBoston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA. (författare)
  • Rodan, Aylin R.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. (författare)
  • Andeen, NicoleOregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. (författare)
  • Hayashi, NorifumiBoston 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. (författare)
  • Williams, BrandiUniv Utah Hlth, Moran Eye Ctr, Salt Lake City, UT USA. (författare)
  • Revelo, Monica P.Univ Utah Hlth, Dept Pathol, Salt Lake City, UT USA. (författare)
  • Clayton, FredUniv Utah Hlth, Dept Pathol, Salt Lake City, UT USA. (författare)
  • Abraham, JoUniv Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA. (författare)
  • Lin, EdwinUniv Utah Hlth, Dept Human Genet, Salt Lake City, UT USA. (författare)
  • Liou, WillisaUniv Utah Hlth, Dept Pathol, Salt Lake City, UT USA. (författare)
  • Zou, Chang-JiangUniv Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA. (författare)
  • Ramkumar, NirupamaUniv Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA. (författare)
  • Cummins, TimUniv Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA. (författare)
  • Wilkey, Daniel W.Univ Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA. (författare)
  • Kawalit, IssaInt Renal Care Assoc, Amman, Jordan. (författare)
  • Herzog, ChristianUniv Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA. (författare)
  • Storey, AaronUniv Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA. (författare)
  • Edmondson, RickUniv Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA. (författare)
  • Sjöberg, RonaldKTH,Affinitets-proteomik(Swepub:kth)u1j1wpi6 (författare)
  • Yang, TianxinUniv 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. (författare)
  • Chien, JeremyUniv Calif Davis Hlth, Dept Biochem & Mol Med, Davis, CA USA. (författare)
  • Merchant, MichaelUniv Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA. (författare)
  • Arthur, JohnUniv Arkansas Med Sci, Internal Med Dept, Nephrol Div, Little Rock, AR USA. (författare)
  • Klein, JonUniv Louisville, Dept Med, Div Nephrol & Hypertens, Clin Prote Lab,Sch Med, Louisville, KY USA.;Robley Rex Vet Adm Med Ctr, Louisville, KY USA. (författare)
  • Larsen, ChrisArkana Labs, Little Rock, AR USA. (författare)
  • Beck, Laurence H.Boston Med Ctr, Dept Med, Sect Nephrol, Rm 536,650 Albany St, Boston, MA 02118 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA. (författare)
  • Univ Utah Hlth, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.Arkana Labs, Little Rock, AR USA. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of the American Society of Nephrology: American Society of Nephrology (ASN)32:7, s. 1666-16811046-66731533-3450

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