Endogenous Antibody Responses to SARS-CoV-2 in Patients With Mild or Moderate COVID-19 Who Received Bamlanivimab Alone or Bamlanivimab and Etesevimab Together

BackgroundNeutralizing monoclonal antibodies (mAbs) to SARS-CoV-2 are clinically efficacious when administered early, decreasing hospitalization and mortality in patients with mild or moderate COVID-19. We investigated the effects of receiving mAbs (bamlanivimab alone and bamlanivimab and etesevimab together) after SARS-CoV-2 infection on the endogenous immune response.MethodsLongitudinal serum samples were collected from patients with mild or moderate COVID-19 in the BLAZE-1 trial who received placebo (n=153), bamlanivimab alone [700 mg (n=100), 2800 mg (n=106), or 7000 mg (n=98)], or bamlanivimab (2800 mg) and etesevimab (2800 mg) together (n=111). A multiplex Luminex serology assay measured antibody titers against SARS-CoV-2 antigens, including SARS-CoV-2 protein variants that evade bamlanivimab or etesevimab binding, and SARS-CoV-2 pseudovirus neutralization assays were performed.ResultsThe antibody response in patients who received placebo or mAbs had a broad specificity. Titer change from baseline against a receptor-binding domain mutant (Spike-RBD E484Q), as well as N-terminal domain (Spike-NTD) and nucleocapsid protein (NCP) epitopes were 1.4 to 4.1 fold lower at day 15-85 in mAb recipients compared with placebo. Neutralizing activity of day 29 sera from bamlanivimab monotherapy cohorts against both spike E484Q and beta variant (B.1.351) were slightly reduced compared with placebo (by a factor of 3.1, p=0.001, and 2.9, p=0.002, respectively). Early viral load correlated with the subsequent antibody titers of the native, unmodified humoral response (p<0.0001 at Day 15, 29, 60 and 85 for full-length spike).ConclusionsPatients with mild or moderate COVID-19 treated with mAbs develop a wide breadth of antigenic responses to SARS-CoV-2. Small reductions in titers and neutralizing activity, potentially due to a decrease in viral load following mAb treatment, suggest minimal impact of mAb treatment on the endogenous immune response.

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Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients

Viruses ◽

10.3390/v13071347 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1347

Author(s):

Claudia Maria Trombetta ◽

Serena Marchi ◽

Simonetta Viviani ◽

Alessandro Manenti ◽

Linda Benincasa ◽

...

Keyword(s):

Natural Infection ◽

Neutralizing Antibody ◽

Original Strain ◽

Immune Protection ◽

Serum Samples ◽

Symptomatic Infection ◽

Neutralizing Activity ◽

The United Kingdom ◽

Antibody Titers ◽

Pandemic Wave

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

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Immunogenicity of Influenza Vaccination in Patients with Non-Hodgkin Lymphoma: Final Report after Two Epidemic Seasons.

Blood ◽

10.1182/blood.v108.11.4598.4598 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4598-4598

Author(s):

Piotr Centkowski ◽

Lidia B. Brydak ◽

Magdalena Machala ◽

Ewa Kalinka ◽

Maria Blasinska-Morawiec ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza Vaccination ◽

Hodgkin Lymphoma ◽

Geometric Mean ◽

Humoral Response ◽

Final Report ◽

Healthy Controls ◽

Serum Samples ◽

Non Hodgkin Lymphoma ◽

Antibody Titers

Abstract Vaccination against influenza is recommended for immunocompromised individuals. However, there is little information concerning the efficacy of vaccination in patients (pts) with non-Hodgkin lymphoma (NHL). The purpose of this study was to assess humoral response to standard intramuscular trivalent subunit influenza vaccine in pts with NHL as compared to healthy subjects. In two consecutive epidemic seasons, 2003/2004 and 2004/2005, 163 pts and 92 healthy controls were vaccinated. Antibody titers to hemagglutinin (HA) and neuraminidase (NA) were measured in serum samples collected before vaccination, and 1 and 6 months apart. Changes in the hemagglutination inhibition (HAI) and neuraminidase inhibition (NII) antibody titers were assessed by comparing geometric mean titers and mean fold increases to baseline values and by comparing changes in the HA seroconversion and seroprotection rates. Pts who received influenza vaccine during 2003/2004 season had after one month increases in the geometric mean titers by a factor of 8,64–26,60 for HI and 6,93–12,66 for NI, as compared with respective increases by a factor of 9,12–24,41 and 4,83–10,31 for the healthy controls. At one month after vaccination seroprotection and seroresponse rates were similar in the two groups, ranging from 68,42 to 84,21 % and 71,93 to 94,74 % in NHL and 66,67–82,22 % and 62,22–86,67 % in controls, respectively. After six months, seroprotection and seroresponse rates had decreased in NHL group to 31,91–38,30% and 46,81–72,34%, respectively. Pts who received influenza vaccine during 2004/2005 season had after 1 month increases in the geometric mean titers by a factor of 38,76–41,49 for HI and 26,59–30,31 for NI, as compared with respective increases by a factor of 81,19–104,32 and 52,16–54,52 for the healthy controls. Seroprotection and seroresponse rates were lower in the former group, ranging from 62,11 to 65,26 % and 74,47 to 77,66 %, respectively. After six months, these parameters had decreased to 24,72–31,46% and 57,30–59,55%, respectively. In both studied seasons, pts achieved titres of functional antibodies greater than the protective threshold, irrespective of the previous chemotherapy administration. The results of this study indicate that standard influenza vaccination induces sufficient immune responses in pts with NHL. Previous chemotherapy adminstration seems to have no impact on the efficacy of vaccination.

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Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

10.1101/2021.06.02.21257975 ◽

2021 ◽

Author(s):

Carlos A Sariol ◽

Petraleigh Pantoja ◽

Crisanta Serrano-Collazo ◽

Tiffant Rosa-Arocho ◽

Albersy Armina ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Vaccine Dose ◽

Humoral Response ◽

Neutralizing Antibody ◽

Viral Neutralization ◽

Neutralizing Activity ◽

Robust Immune Response

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

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Bacillus Subtilis Spores as Delivery System for Nasal Plasmodium Falciparum Circumsporozoite Surface Protein Immunization in a Murine Model

10.21203/rs.3.rs-777937/v1 ◽

2021 ◽

Author(s):

Maria Edilene M. de Almeida ◽

Késsia Caroline Souza Alves ◽

Maria Gabriella Santos de Vasconcelos ◽

Thiago Serrão Pinto ◽

Juliane Corrêa Glória ◽

...

Keyword(s):

Immune Response ◽

Public Health Problem ◽

Surface Protein ◽

Humoral Response ◽

Serum Samples ◽

Th2 Immune Response ◽

The World ◽

Protein Immunization ◽

Vaccine Carrier ◽

Full Protection

Abstract Malaria remains a widespread public health problem in tropical and subtropical regions around the world, and there is still no vaccine available for full protection. In recent years, it has been observed that spores of Bacillus subtillis can act as a vaccine carrier and adjuvant, promoting an elevated humoral response after co-administration with antigens either coupled or integrated to their surface. In our study, B. subtillis spores from the KO7 strain were used to couple the recombinant CSP protein of P. falciparum (rPfCSP), and the nasal humoral-induced immune response in Balb/C mice was evaluated. Our results demonstrate that the spores coupled to rPfCSP increase the immunogenicity of the antigen, which induces high levels of serum IgG, and with balanced Th1/Th2 immune response, being detected antibodies in serum samples for 250 days. Therefore, the use of B. subtilis spores appears to be promising for use as an adjuvant in a vaccine formulation.

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Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients

Journal of Clinical Medicine ◽

10.3390/jcm10215153 ◽

2021 ◽

Vol 10 (21) ◽

pp. 5153

Author(s):

Seyedesomaye Jasemi ◽

Gian Luca Erre ◽

Maria Luisa Cadoni ◽

Marco Bo ◽

Leonardo A. Sechi

Keyword(s):

Rheumatoid Arthritis ◽

Immune Response ◽

Humoral Immune Response ◽

Humoral Response ◽

Human Endogenous Retrovirus ◽

Serum Samples ◽

Humoral Immune ◽

Bivariate Correlation ◽

Microbial Biomarkers ◽

Significant Difference

Background/Objective: Chronic humoral immune response against multiple microbial antigens may play a crucial role in the etiopathogenesis of rheumatoid arthritis (RA). We aimed to assess the prevalence and magnitude of antibody response against various bacterial and viral immunogen peptides in the sera of RA patients compared with the general population. Methods: Polyclonal IgG antibodies (Abs) specific for peptides derived from Porphyromonas gingivalis (RgpA, Kpg), Aggregatibacter actinomycetemcomitans (LtxA1, LtxA2), Mycobacterium avium subsp. paratuberculosis (MAP4027), Epstein–Barr virus (EBNA1, EBVBOLF), and human endogenous retrovirus (HERV-W env-su) were detected by ELISA in serum samples from 148 consecutive RA patients and 148 sex and age-matched healthy controls (HCs). In addition, the presence of a relationship between the positivity and the titer of antibodies and RA descriptors was explored by bivariate correlation analysis. Results: RA patients exhibit a higher prevalence of humoral immune response against all tested peptides compared to HCs with a statically significant difference for MAP4027 (30.4% vs. 10.1%), BOLF (25.7% vs. 8.1%), RgpA (24.3% vs. 9.4%), HERV W-env (20.3% vs. 9.4%), and EBNA1 (18.9% vs. 9.4%) peptides. Fifty-three (35.8%) out of 148 RA serum and 93 (62.8%) out of 148 HCs were negative for all pathogen-derived peptides. There was a significant correlation between OD values obtained by ELISA test against all peptides (p < 0.0001). We also found an increased titer and prevalence of Abs against LtxA1 and LtxA2 in seropositive vs. seronegative RF (p = 0.019, p = 0.018). Conclusion: This study demonstrates a significantly increased humoral response against multiple pathogens in patients with RA and implies that they could be an important factor in the pathogenesis of the disease. Therefore, the role of each individual pathogen in RA needs to be further investigated.

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Expression of Antibodies Directed to Paracoccidioides brasiliensis Glycosphingolipids during the Course of Paracoccidioidomycosis Treatment

Clinical and Vaccine Immunology ◽

10.1128/cvi.00285-06 ◽

2006 ◽

Vol 14 (2) ◽

pp. 150-156 ◽

Cited By ~ 18

Author(s):

Silvio Bertini ◽

Arnaldo L. Colombo ◽

Helio K. Takahashi ◽

Anita H. Straus

Keyword(s):

Immune Response ◽

Paracoccidioides Brasiliensis ◽

Immunoglobulin M ◽

Antifungal Treatment ◽

Primary Immune Response ◽

Enzyme Linked Immunosorbent Assay ◽

Carbohydrate Structure ◽

Dimorphic Fungus ◽

Serum Samples ◽

Antibody Titers

ABSTRACT Paracoccidioidomycosis (PCM) is a granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. The immunoglobulin classes and isotypes of antibodies directed to acidic glycosphingolipids (GSLs) and glucosylceramide of P. brasiliensis were determined by enzyme-linked immunosorbent assay of sera from 31 PCM patients. The reactivities of 38 serum samples were analyzed by considering the stage of treatment: before antifungal treatment (n = 10), during 1 to 4 months of treatment (T1-4; n = 9), during 5 to 12 months of treatment (T5-12; n = 9), and posttreatment (PT; n = 10). Sera from healthy subjects (n = 12) were used as controls. Only the GSL Pb-1 antigen, which presents the carbohydrate structure Galfβ1-6(Manα1-3)Manβ1, was reactive with the PCM patient sera. The PCM patient sera did not react with Pb-2, which lacks the Galf residue and which is considered the biosynthetic precursor of Pb-1, indicating that the Galf residue is essential for antibody reactivity. The Pb-1 glycolipid from nontreated patients elicited a primary immune response with immunoglobulin M (IgM) production and subsequent switching to IgG1 production. The IgG1 titer increased after the start of antifungal treatment (T1-4 group), and general decreases in the anti-Pb-1 antibody titers were observed after 5 months of treatment (T5-12 and PT groups). The Pb-1 antigen, an acidic GSL with terminal Galf residue, has potential application as an elicitor of the host immune response in patients with PCM.

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From infection to immunity: understanding the response to SARS-CoV2 through in-silico modeling

10.1101/2020.12.20.423670 ◽

2020 ◽

Author(s):

Filippo Castiglione ◽

Debashrito Deb ◽

Anurag P. Srivastava ◽

Pietro Liò ◽

Arcangelo Liso

Keyword(s):

Immune Response ◽

Viral Load ◽

Computational Modeling ◽

In Silico ◽

Vaccine Development ◽

Real Life ◽

Humoral Response ◽

Immune Competence ◽

Modeling Framework ◽

The Impact

AbstractBackgroundImmune system conditions of the patient is a key factor in COVID-19 infection survival. A growing number of studies have focused on immunological determinants to develop better biomarkers for therapies.AimThe dynamics of the insurgence of immunity is at the core of the both SARS-CoV-2 vaccine development and therapies. This paper addresses a fundamental question in the management of the infection: can we describe the insurgence (and the span) of immunity in COVID-19? The in-silico model developed here answers this question at individual (personalized) and population levels.We simulate the immune response to SARS-CoV-2 and analyze the impact of infecting viral load, affinity to the ACE2 receptor and age in the artificially infected population on the course of the disease.MethodsWe use a stochastic agent-based immune simulation platform to construct a virtual cohort of infected individuals with age-dependent varying degree of immune competence. We use a parameter setting to reproduce known inter-patient variability and general epidemiological statistics.ResultsWe reproduce in-silico a number of clinical observations and we identify critical factors in the statistical evolution of the infection. In particular we evidence the importance of the humoral response over the cytotoxic response and find that the antibody titers measured after day 25 from the infection is a prognostic factor for determining the clinical outcome of the infection.Our modeling framework uses COVID-19 infection to demonstrate the actionable effectiveness of simulating the immune response at individual and population levels. The model developed is able to explain and interpret observed patterns of infection and makes verifiable temporal predictions.Within the limitations imposed by the simulated environment, this work proposes in a quantitative way that the great variability observed in the patient outcomes in real life can be the mere result of subtle variability in the infecting viral load and immune competence in the population.In this work we i) show the power of model predictions, ii) identify the clinical end points that could be more suitable for computational modeling of COVID-19 immune response, iii) define the resolution and amount of data required to empower this class of models for translational medicine purposes and, iv) we exemplify how computational modeling of immune response provides an important light to discuss hypothesis and design new experiments.

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Immune Response to Recombinant Capsid Proteins of Adenovirus in Humans: Antifiber and Anti-Penton Base Antibodies Have a Synergistic Effect on Neutralizing Activity

Journal of Virology ◽

10.1128/jvi.72.3.2388-2397.1998 ◽

1998 ◽

Vol 72 (3) ◽

pp. 2388-2397 ◽

Cited By ~ 145

Author(s):

Hanne Gahéry-Ségard ◽

Françoise Farace ◽

Dominique Godfrin ◽

Jesintha Gaston ◽

Renée Lengagne ◽

...

Keyword(s):

Gene Therapy ◽

Immune Response ◽

Gene Transfer ◽

Synergistic Effect ◽

Humoral Response ◽

Viral Capsid ◽

Penton Base ◽

Strong Immune Response ◽

Neutralizing Activity ◽

Humoral Immune

ABSTRACT Replication-deficient adenovirus used in humans for gene therapy induces a strong immune response to the vector, resulting in transient recombinant protein expression and the blocking of gene transfer upon a second administration. Therefore, in this study we examined in detail the capsid-specific humoral immune response in sera of patients with lung cancer who had been given one dose of a replication-defective adenovirus. We analyzed the immune response to the three major components of the viral capsid, hexon (Hx), penton base (Pb), and fiber (Fi). A longitudinal study of the humoral response assayed on adenovirus particle-coated enzyme-linked immunosorbent assay plates showed that patients had preexisting immunity to adenovirus prior to the administration of adenovirus–β-gal. The level of the response increased in three patients after adenovirus administration and remained at a maximum after three months. One patient had a strong immune response to adenovirus prior to treatment, and this response was unaffected by adenovirus administration. Sera collected from the patients were assayed for recognition of each individual viral capsid protein to determine more precisely the molecular basis of the humoral immune response. Clear differences existed in the humoral response to the three major components of the viral capsid in serum from humans. Sequential appearance of these antibodies was observed: anti-Fi antibodies appeared first, followed by anti-Pb antibodies and then by anti-Hx antibodies. Moreover, anti-Fi antibodies preferentially recognized the native trimeric form of Fi protein, suggesting that they recognized conformational epitopes. Our results showed that sera with no neutralizing activity contained only anti-Fi antibodies. In contrast, neutralizing activity was only obtained with sera containing anti-Fi and anti-Pb antibodies. More importantly, we showed that anti-native Fi and anti-Pb antibodies had a synergistic effect on neutralization. The application of these conclusions to human gene therapy with recombinant adenovirus should lead to the development of strategies to overcome the formation of such neutralization antibodies, which have been shown to limit the efficacy of gene transfer in humans.

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The effect of anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, on endogenous immune response to COVID-19 vaccination

10.1101/2021.12.15.21267605 ◽

2021 ◽

Author(s):

Robert J. Benschop ◽

Jay L. Tuttle ◽

Lin Zhang ◽

Josh Poorbaugh ◽

Nicole L. Kallewaard ◽

...

Keyword(s):

Monoclonal Antibody ◽

Immune Response ◽

Monoclonal Antibodies ◽

Antibody Response ◽

Nursing Home Residents ◽

Risk Category ◽

Serum Samples ◽

Robust Immune Response ◽

Vaccine Type ◽

Endogenous Immune Response

As the COVID-19 pandemic evolves, and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of SARS-CoV-2 infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of six months, serum samples were collected from the prevention population (nursing home residents and staff) enrolled in the BLAZE-2 clinical trial who had received either bamlanivimab (4200 mg) or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines, as part of the US vaccination program. This post-hoc analysis assessed the immune response to vaccination for the subset of participants (N=135) without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not significantly bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo participants mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk-category and vaccine type, with any observed differences unlikely to be clinically meaningful. These findings are pertinent for informing public health policy with results that suggest a complementary role for COVID-19 monoclonal antibodies (mAbs) with COVID-19 vaccines and that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 mAb infusion.

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Immune Response to Enterococcus gallinarum in Lupus Patients Is Associated With a Subset of Lupus-Associated Autoantibodies

Frontiers in Immunology ◽

10.3389/fimmu.2021.635072 ◽

2021 ◽

Vol 12 ◽

Author(s):

Harini Bagavant ◽

Antonina M. Araszkiewicz ◽

Jessica K. Ingram ◽

Katarzyna Cizio ◽

Joan T. Merrill ◽

...

Keyword(s):

Immune Response ◽

Lupus Erythematosus ◽

Surrogate Marker ◽

Healthy Controls ◽

Igg Antibodies ◽

Serum Samples ◽

Specific Subset ◽

Antibody Titers ◽

Enterococcus Gallinarum ◽

Ribosomal P

Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently, Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence of E. gallinarum exposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarum IgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarum antibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive with E. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarum IgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarum titers were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarum titers correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive to E. gallinarum. In SLE patients, the immune response to E. gallinarum was associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence that E. gallinarum may be a pathobiont for SLE in susceptible individuals.

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