Evidence map›Paper›PMID 31270218›Full record

ArticleNeurology2019

Exploratory proteomic analysis implicates the alternative complement cascade in primary CNS vasculitis.

Caleigh Mandel-Brehm, Hanna Retallack, Giselle M Knudsen, Alex Yamana, Rula A Hajj-Ali, Leonard H Calabrese, Tarik Tihan, Hannah A Sample, Kelsey C Zorn, Mark P Gorman and 8 more

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In one paragraph

Article in Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Primary Angiitis of the CNS: A Systematic Review and Meta-analysis.Neurology(R) neuroimmunology & neuroinflammation · 2021
    Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Caleigh Mandel-BrehmFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Hanna RetallackFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Giselle M KnudsenFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Alex YamanaFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Rula A Hajj-AliFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Leonard H CalabreseFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Tarik TihanFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Hannah A SampleFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Kelsey C ZornFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Mark P GormanFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Jennifer Madan CohenFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Antoine G SreihFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Jacqueline F MarcusFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
S Andrew JosephsonFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Vanja C DouglasFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Jeffrey M GelfandFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Michael R WilsonFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA.
Joseph L DeRisiFrom the Departments of Biochemistry and Biophysics (C.M.-B., H.R., H.A.S., K.C.Z., J.L.D.), Pharmaceutical Chemistry (G.M.K., A.Y.), Pathology and Laboratory Medicine (T.T.), and Neurology (S.A.J., V.C.D., J.M.G., M.R.W.), University of California, San Francisco; Department of Rheumatology/Immunology (R.A.H.-A., L.H.C.), Cleveland Clinic, OH; Department of Neurology (M.P.G.), Boston Children's Hospital, MA; Division of Neurology (J.M.C.), Connecticut Children's Medical Center, Hartford; Division of Rheumatology (A.G.S.), University of Pennsylvania, Philadelphia; Kaiser Permanente (J.F.M.), San Francisco Medical Center; UCSF Weill Institute for Neurosciences (S.A.J., V.C.D., J.M.G., M.R.W.); and Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA. joe@derisilab.ucsf.edu.

Funding

Microbial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5M
Next-Generation Diagnostics for Acute EncephalitisK08NS096117 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILSON, MICHAEL R · 2017 to 2021
$999k
NIAID NIH HHS T32 AI060537NINDS NIH HHS K08 NS096117
6 · The paper itself

Abstract

objectiveTo identify molecular correlates of primary angiitis of the CNS (PACNS) through proteomic analysis of CSF from a biopsy-proven patient cohort.

methodsUsing mass spectrometry, we quantitatively compared the CSF proteome of patients with biopsy-proven PACNS (n = 8) to CSF from individuals with noninflammatory conditions (n = 11). Significantly enriched molecular pathways were identified with a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.5 and concordant Benjamini-Hochberg-adjusted

resultsCompared to noninflammatory controls, 283 proteins were differentially expressed in the CSF of patients with PACNS, with significant enrichment of the complement cascade pathway (C4-binding protein, CD55, CD59, properdin, complement C5, complement C8, and complement C9) and neural cell adhesion molecules. A subset of clinically relevant findings were validated by Western blot and commercial ELISA.

conclusionsIn this exploratory study, we found evidence of deregulation of the alternative complement cascade in CSF from biopsy-proven PACNS compared to noninflammatory controls. More specifically, several regulators of the C3 and C5 convertases and components of the terminal cascade were significantly altered. These preliminary findings shed light on a previously unappreciated similarity between PACNS and systemic vasculitides, especially anti-neutrophil cytoplasmic antibody-associated vasculitis. The therapeutic implications of this common biology and the diagnostic and therapeutic utility of individual proteomic findings warrant validation in larger cohorts.

Indexed as

ProteomicsAdolescentAdultBiopsyBrainCase-Control StudiesCD55 AntigensCD59 AntigensCohort StudiesComplement C4b-Binding ProteinComplement C5Complement C8Complement C9Complement Pathway, AlternativeComplement System ProteinsFemaleCD55 AntigensCD59 AntigensCD59 protein, humanComplement C4b-Binding ProteinComplement C5Complement C8Complement C9Complement System ProteinsNeural Cell Adhesion MoleculesProperdin

Identifiers

PMID31270218
PMCPMC6693432

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