Serum autoantibodyome reveals that healthy individuals share common autoantibodies

Shome, Mahasish; Chung, Yunro; Chavan, Rohidas; Park, Jin G.; Qiu, Ji; LaBaer, Joshua

doi:10.1016/j.celrep.2022.110873

Cited by 33 publications

(35 citation statements)

References 36 publications

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“…Autoimmune responses can be found in healthy individuals and could explain autoantibodies in the uninfected group, given only one individual reported a known autoimmune history ( 40 , 41 ). Indeed, a recent study investigated the “autoantibodyome” amongst healthy and disease cohorts and identified 77 common autoantibodies within the healthy individuals ( 42 ). Amongst the thousands of human proteins measured against, none of the 102 disease specific autoantigens measured in this study were among the 77 common targets.…”

Section: Discussionmentioning

confidence: 99%

Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes

et al. 2022

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Autoantibodies to multiple targets are found during acute COVID-19. Whether all, or some, persist after 6 months, and their correlation with sustained anti-SARS-CoV-2 immunity, is still controversial. Herein, we measured antibodies to multiple SARS-CoV-2 antigens (Wuhan-Hu-1 nucleoprotein (NP), whole spike (S), spike subunits (S1, S2 and receptor binding domain (RBD)) and Omicron spike) and 102 human proteins with known autoimmune associations, in plasma from healthcare workers 8 months post-exposure to SARS-CoV-2 (n=31 with confirmed COVID-19 disease and n=21 uninfected controls (PCR and anti-SARS-CoV-2 negative) at baseline). IgG antibody responses to SARS-CoV-2 antigens were significantly higher in the convalescent cohort than the healthy cohort, highlighting lasting antibody responses up to 8 months post-infection. These were also shown to be cross-reactive to the Omicron variant spike protein at a similar level to lasting anti-RBD antibodies (correlation r=0.89). Individuals post COVID-19 infection recognised a common set of autoantigens, specific to this group in comparison to the healthy controls. Moreover, the long-term level of anti-Spike IgG was associated with the breadth of autoreactivity post-COVID-19. There were further moderate positive correlations between anti-SARS-CoV-2 responses and 11 specific autoantigens. The most commonly recognised autoantigens were found in the COVID-19 convalescent cohort. Although there was no overall correlation in self-reported symptom severity and anti-SARS-CoV-2 antibody levels, anti-calprotectin antibodies were associated with return to healthy normal life 8 months post infection. Calprotectin was also the most common target for autoantibodies, recognized by 22.6% of the overall convalescent cohort. Future studies may address whether, counter-intuitively, such autoantibodies may play a protective role in the pathology of long-COVID-19.

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Section: Discussionmentioning

confidence: 99%

Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes

et al. 2022

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“…The Malmstrom group used quantitative and structural mass spectrometry to demonstrate that Streptococcus pyogenes , a human-specific Gram-positive bacterium, establishes serotype-specific interactions with human plasma proteins as a likely means to inhibit immune responses during mucosal and systemic infections . Integrating information from protein microarray data, the LaBaer group identified a set of common autoantibodies present in healthy individuals, without gender preference, thereby providing critical information for determining possible false positives within reported disease-related biomarkers . In response to the ongoing pandemic, the ID team joined members of other B/D-HPP teams (noted above) to elucidate the biology and pathology of SARS-CoV-2 infection.…”

Section: Highlights From the B/d-hppmentioning

confidence: 99%

The 2022 Report on the Human Proteome from the HUPO Human Proteome Project

et al. 2022

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The 2022 Metrics of the Human Proteome from the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 407 (93.2%) of the 19 750 predicted proteins coded in the human genome, a net gain of 50 since 2021 from data sets generated around the world and reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 78 from 1421 to 1343. This represents continuing experimental progress on the human proteome parts list across all the chromosomes, as well as significant reclassifications. Meanwhile, applying proteomics in a vast array of biological and clinical studies continues to yield significant findings and growing integration with other omics platforms. We present highlights from the Chromosome-Centric HPP, Biology and Disease-driven HPP, and HPP Resource Pillars, compare features of mass spectrometry and Olink and Somalogic platforms, note the emergence of translation products from ribosome profiling of small open reading frames, and discuss the launch of the initial HPP Grand Challenge Project, "A Function for Each Protein".

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“…These could be natural autoantibodies (which are produced by the immune system to intentionally target self-antigens) that aid in regulating normal homeostatic processes [42], clearing cellular debris and other waste products from dying cells [43], catalyzing enzymatic reactions [44], and training the adaptive immune system to protect against self-antigens that may induce a severe immune response [45]. Notably, the protective function of natural autoantibodies has been generally ascribed to the IgM class [46]; nevertheless, it is now beginning to be discovered that an IgG autoantibody repertoire exists in the blood of healthy individuals [47,48] that is considered to be highly individualized and stable in adults [47]. Examining whether the IgG autoantibodies lower in RA subgroups play any causal role in attenuating RA severity, or whether any of these may be utilized for therapeutic purposes, would be appealing topics for future studies.…”

Section: Discussionmentioning

confidence: 99%

Patients with ACPA-positive and ACPA-negative Rheumatoid Arthritis Show Different Serological Autoantibody Repertoires and Autoantibody Associations with Disease Activity

Cunningham

Hur

Gupta

et al. 2022

Preprint

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Objectives. Patients with rheumatoid arthritis (RA) can test either positive or negative for anti-citrullinated protein antibodies (ACPA), and are thereby ACPA-positive (ACPA+) or ACPA-negative (ACPA-), respectively. Through comprehensive profiling of autoantibodies in serum, we aimed to identify autoantibodies that are differentially abundant between patients with ACPA+ RA and ACPA- RA, and also those that are significantly associated with clinical disease activity. Methods. Serum was collected from patients with ACPA+ RA (n = 32), ACPA- RA (n = 30), and healthy controls (n = 30). Sengenics Immunome™ protein microarray was used to screen for over 1,600 IgG autoantibodies against native, unmodified human proteins from each serum sample. Autoantibody profiles were compared between each RA subgroup and controls to identify differentially abundant autoantibodies (P < 0.05, Mann-Whitney U test; |Cliff′s delta (d)| > 0.33). Additionally, the relationship between RA patients′ autoantibody abundances and Clinical Disease Activity Index (CDAI) was examined for correlations between serum autoantibodies and disease activity (|Spearman′s ρ| > 0.4 and P < 0.01). Results. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA- RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies higher in ACPA+ RA patients and ACPA- RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons. On the other hand, we found 30 and 25 autoantibodies lower in ACPA+ RA and ACPA- RA, respectively, of which eight autoantibodies were common in both comparisons. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with CDAI, but associate differently depending on the presence or absence of ACPA. Conclusions. ACPA status in patients with RA determines not only the composition of the serum autoantibody repertoire, but also the correlative relationships between autoantibodies and disease activity. Notably, many of the autoantibodies identified herein were reported for the first time. Our findings warrant further investigation into the immunological differences between these two RA subgroups, and shed new light on the possible need for different treatment approaches.

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Serum autoantibodyome reveals that healthy individuals share common autoantibodies

Cited by 33 publications

References 36 publications

Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes

Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes

The 2022 Report on the Human Proteome from the HUPO Human Proteome Project

Patients with ACPA-positive and ACPA-negative Rheumatoid Arthritis Show Different Serological Autoantibody Repertoires and Autoantibody Associations with Disease Activity

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