AUTHOR=Rigat Fabio , Bartolini Erika , Dalsass Mattia , Kumar Neha , Marchi Sara , Speziale Pietro , Maione Domenico , Chen Luqiu , Romano Maria Rosaria , Alegre Maria-Luisa , Bagnoli Fabio , Daum Robert S. , David Michael Z. 

TITLE=Retrospective Identification of a Broad IgG Repertoire Differentiating Patients With S. aureus Skin and Soft Tissue Infections From Controls

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00114

DOI=10.3389/fimmu.2019.00114

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> Although the relevance of humoral immunity for protection against <italic>S. aureus</italic> skin and soft tissue infections (SSTIs) has been suggested by several animal and human studies, the question of which human antibodies may be protective has so far impeded the development of a safe and effective vaccine. Because most adults have developed certain anti-<italic>S. aureus</italic> antibodies due to <italic>S. aureus</italic> colonization or infection, we hypothesized that the titers of antibodies to <italic>S. aureus</italic> in uninfected controls would differ from those in infected patients and would also differ in infected patients from the time of acute infection to a 40-day convalescent serum.</p><p><bold>Methods:</bold> To test these hypotheses, we measured human antibody levels against a panel of 134 unique antigens comprising the <italic>S. aureus</italic> surfome and secretome in subjects with active culture-confirmed <italic>S. aureus</italic> SSTIs (cases) and in controls with no infection, using a novel <italic>S. aureus</italic> protein microarray.</p><p><bold>Results:</bold> Most <italic>S. aureus</italic> SSTI patients (<italic>n</italic> = 60) and controls (<italic>n</italic> = 142) had antibodies to many of the tested <italic>S. aureus</italic> antigens. Univariate analysis showed statistically weak differences in the IgG levels to some antigens in the SSTI patient (case) sera compared with controls. Antibody levels to most tested antigens did not increase comparing acute with 40-day serum. Multiple logistic regression identified a rich subset of antigens that, by their antibody levels, together correctly differentiated all cases from all controls.</p><p><bold>Conclusions:</bold> Antibodies directed against <italic>S. aureus</italic> antigens were present both in patients with <italic>S. aureus</italic> SSTIs and in uninfected control patients. We found that SSTI patients and controls could be distinguished only based on differences in antibody levels to many staphylococcal surface and secreted antigens. Our results demonstrate that in the studied population, the levels of anti-<italic>S. aureus</italic> antibodies appear largely fixed, suggesting that there may be some level of unresponsiveness to natural infection.</p>