title: Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus.
abstract: Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor-binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor-binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell-activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α-driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE.
authors.forename: Jordan V
authors.initials: JV
authors.lastname: Price
authors.forename: David J
authors.initials: DJ
authors.lastname: Haddon
authors.forename: Dodge
authors.initials: D
authors.lastname: Kemmer
authors.forename: Guillaume
authors.initials: G
authors.lastname: Delepine
authors.forename: Gil
authors.initials: G
authors.lastname: Mandelbaum
authors.forename: Justin A
authors.initials: JA
authors.lastname: Jarrell
authors.forename: Rohit
authors.initials: R
authors.lastname: Gupta
authors.forename: Imelda
authors.initials: I
authors.lastname: Balboni
authors.forename: Eliza F
authors.initials: EF
authors.lastname: Chakravarty
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Shum
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
authors.forename: Mickie H
authors.initials: MH
authors.lastname: Cheng
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Browne
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Emily C
authors.initials: EC
authors.lastname: Baechler
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Utz
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007249:Inflammation; D016898:Interferon-alpha / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D009164:Mycobacterium Infections / Q000097:blood / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000276:immunology; D040081:Protein Array Analysis; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D053264:B-Cell Activating Factor; D016207:Cytokines; D007074:Immunoglobulin G; D016898:Interferon-alpha; D011994:Recombinant Proteins; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse