Effects of Age, Sex, Serostatus and Underlying Comorbidities on Humoral Response Post-SARS-CoV-2 Pfizer-BioNTech Vaccination: A Systematic Review

With the advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences of the Coronavirus Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses to prevent SARS-CoV-2 infections. Despite effectiveness and safety, inter-individual immune response heterogeneity has been observed in recipients of mRNA-based vaccines. As a novel disease, the specific immune response mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral response plays a crucial role in affording immunoprotection and preventing debilitating sequelae from COVID-19. As such this paper focused on the possible effects of age, sex, serostatus, and comorbidities on humoral response (i.e., total antibodies, IgG and/or IgA) of different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search of literature was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported humoral response to COVID-19 mRNA vaccines. A total of 32 studies was identified and reviewed, and the percent difference of means of reported antibody levels were calculated for comparison. Findings revealed that older individuals, the male sex, seronegativity, and those with more comorbidities mounted less humoral immune response. Given these findings, several recommendations were proposed regarding the current vaccination practices. These include giving additional doses of vaccination for immunocompromised and elderly populations. Another recommendation is conducting clinical trials in giving a combined scheme of mRNA vaccines, protein vaccines, and vector-based vaccines.

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Maternally Derived Antibody Levels Influence on Vaccine Protection against PCV2d Challenge

Animals ◽

10.3390/ani11082231 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2231

Author(s):

István Kiss ◽

Krisztina Szigeti ◽

Zalán G. Homonnay ◽

Vivien Tamás ◽

Han Smits ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Subunit Vaccine ◽

Porcine Circovirus Type ◽

Porcine Circovirus ◽

Vaccine Protection ◽

Humoral Immune ◽

Negative Effect ◽

Antibody Levels

Piglets from a porcine circovirus type 2 (PCV2) stable farm of low and high levels of maternally derived antibodies (MDA) against PCV2 were vaccinated either with a whole virus type or a PCV2 ORF2 antigen-based commercial subunit vaccine at three weeks of age. Two non-vaccinated groups served as low and high MDA positive controls. At four weeks post vaccination, all piglets were challenged with a PCV2d-2 type virus strain and were checked for parameters related to vaccine protection over a four-week observation period. MDA levels evidently impacted the outcome of the PCV2d-2 challenge in non-vaccinated animals, while it did not have a significant effect on vaccine-induced protection levels. The humoral immune response developed faster in the whole virus vaccinates than in the subunit vaccinated pigs in the low MDA groups. Further, high MDA levels elicited a stronger negative effect on the vaccine-induced humoral immune response for the subunit vaccine than for the whole virus vaccine. The group-based oral fluid samples and the group mean viraemia and faecal shedding data correlated well, enabling this simple, and animal welfare-friendly sampling method for the evaluation of the PCV2 viral load status of these nursery piglets.

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VACCINATION AS PRIMARY CONTACT WITH INFLUENZA A AND B VIRUSES

PEDIATRICS ◽

10.1542/peds.3.2.208 ◽

1949 ◽

Vol 3 (2) ◽

pp. 208-213

Author(s):

RAE V. NICHOLAS ◽

WERNER HENLE

Keyword(s):

Immune Response ◽

Antibody Response ◽

Influenza A ◽

Infectious Agents ◽

Older Individuals ◽

Protective Measures ◽

Primary Contact ◽

Small Doses ◽

Antibody Levels ◽

Booster Effect

A single dose of 0.5 ml. of commercially available influenzal virus vaccine injected into children from seven weeks to three years of age produced antibodies in about 70%. Resulting antibody levels in the children, most of whom were born after the last widespread epidemics of influenza A and B, were distinctly lower than those observed in older individuals who, in all likelihood, had experienced previous contacts with influenzal antigens. Two injections at a week's interval failed to result in a better antibody response in these children in agreement with the experience gained in adults. Increase in the dose of vaccine appears unwarranted now, since the incidence of febrile reactions—all of short duration—exceeded 40%. This inferior antibody response may be the result of several factors: (a) the smaller dose of vaccine which can be safely administered to such children; (b) the possible inferior immune response of the younger individual; and (c) the absence of a basic immunity to the antigens present in most older individuals as a result of previous contacts with influenzal viruses. Although it is impossible to decide among these factors, the booster effect of restimulation with small doses of antigen is a well known phenomenon in protective measures against other infectious agents. It is felt that such a mechanism may well be the explanation for the discrepancies between young children and older individuals in their response to vaccination against influenza.

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Dynamics of humoral immune response in pregnant mares and foals vaccinated with Theileria equi recombinant EMA-2

Pesquisa Veterinária Brasileira ◽

10.1590/1678-5150-pvb-5321 ◽

2018 ◽

Vol 38 (6) ◽

pp. 1105-1109

Author(s):

Alice C. Santos ◽

Fábio P.L. Leite ◽

Ana M. Vianna ◽

Guilherme B. Weege ◽

Ilusca S. Finger ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Fold Increase ◽

Serum Levels ◽

Vaccination Schedule ◽

Theileria Equi ◽

Humoral Immune ◽

Baseline Values ◽

Antibody Levels ◽

First Time

ABSTRACT: Theileria equi is an infectious hemoprotozoan agent of equine piroplasmosis, a disease that has severe economic and sanitary impact internationally. In addition to its common clinical features, piroplasmosis can cause gestational losses and neonatal damage, which makes neonates susceptible to this disease. The aim of this study was to evaluate the dynamics of humoral immune response to recombinant EMA-2 of T. equi in pregnant mares and foals, as well as the transfer of vaccine antibodies through the colostrum ingested by sucking foals. For vaccine production, the EMA-2 expression gene was cloned and expressed in the yeast species, Pichia pastoris. Thirty-six horses were used, of which 18 were pregnant mares and 18 were foals. The mares were divided into control and vaccinated groups, and the vaccinated group received three doses of rEMA-2 every 21 days starting at 300 days of gestation. Foals from vaccinated and control groups were evaluated until the sixth month of life. The production of antibodies by foals on the rEMA-2 vaccination schedule was also evaluated from the second month of life. Foals in the vaccinated group had received three doses of the vaccine every 21 days. The method used to evaluate serum and colostrum samples was indirect ELISA, and plates were sensitized with the rEMA-2 protein. At the end of the vaccination schedule, vaccinated mares showed a 2.3-fold increase in antibody levels when compared to baseline values. The colostrum of vaccinated mares presented antibody levels of 1.0432±0.33. Foals delivered by vaccinated mares presented levels of antibodies greater than those of foals delivered by control mares after their first time sucking (at about twelve hours after birth). Foals vaccinated in the second month of life showed an 8.3-fold increase in antibody levels when compared to baseline values. The vaccination schedule with rEMA-2 was able to stimulate humoral immunity in pregnant mares. Vaccine immunoglobins were concentrated in the colostrum of vaccinated mares and foals delivered by these mares showed an increase in serum levels of vaccine antibodies after the first-time sucking.

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Impact of Binge Alcohol Intoxication on the Humoral Immune Response during Burkholderia spp. Infections

Microorganisms ◽

10.3390/microorganisms7050125 ◽

2019 ◽

Vol 7 (5) ◽

pp. 125

Author(s):

Ryan M. Moreno ◽

Victor Jimenez ◽

Fernando P. Monroy

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Opportunistic Infections ◽

Alcohol Intoxication ◽

Experimental Studies ◽

Adaptive Immune System ◽

Humoral Response ◽

Humoral Immune ◽

Healthy Humans ◽

The Impact

Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Currently, no experimental studies have investigated the effects of binge alcohol on the adaptive immune system during an active infection. In this study, we used B. thailandensis and B. vietnamiensis, to investigate the impact of a single binge alcohol episode on the humoral response during infection. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking (4.4 g/kg) or PBS intraperitoneally 30 min before intranasal infection. Mice infected with B. thailandensis had a 100% survival rate, while those infected with B. vietnamiensis had a 33% survivability rate when a binge alcohol dose was administered. B. thailandensis was detected in blood of mice administered alcohol at only 7 days post infection (PI), while those infected with B. vietnamiensis and receiving alcohol were found throughout the 28-day infection as well as in tissues at day 28 PI. Binge alcohol elevated IgM and delayed IgG specific to the whole cell lysate (WCL) of B. vietnamiensis but not B. thailandensis infections. Differences in immunogenicity of B. pseudomallei near-neighbors provide a framework for novel insights into the effects of binge alcohol’s suppression of the humoral immune response that can cause opportunistic infections in otherwise healthy hosts.

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The expression of an intraspecific aggressive reaction in the face of a stressor agent alters the immune response in rats

Brazilian Journal of Biology ◽

10.1590/s1519-69842005000200003 ◽

2005 ◽

Vol 65 (2) ◽

pp. 203-209 ◽

Cited By ~ 9

Author(s):

J. M. Barreto-Medeiros ◽

E. G. Feitoza ◽

K. Magalhães ◽

R. R. da Silva ◽

F. M. Manhães-de-Castro ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Humoral Response ◽

Aggressive Response ◽

Control Group ◽

Blood Samples ◽

Humoral Immune ◽

The Face ◽

Intraspecific Aggressiveness ◽

Specific Humoral Response

The repercussion on the immune response of the expression of intraspecific aggressiveness in the face of a stressor agent was investigated in rats. Ninety-day-old animals were divided into three groups: the control group (only immunological measurements were performed), the foot-shock (FS) (animals individually receiving FS), and the intraspecific aggressive response (IAR) group (animals receiving FS and presenting IAR). For immunological measurements, blood samples were collected promptly at 7 and 15 days after FS or IAR. The FS reduced the total leukocyte amount presented. However, aggressiveness triggered not only reduction of the leukocytes, but also lymphocyte decrease and neutrophil increase. Moreover, an elevation in total leukocytes associated with an increase in the humoral immune response was also observed one week after IAR. In this study, the expression of intraspecific aggressiveness in the face of a stressor seemed to activate the immune system and to potentiate the antigen specific humoral response.

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Should be a Third Dose of BNT162b2 mRNA COVID-19-Vaccine Administered in Patients with Myelofibrosis Under Ruxolitinib?

Blood ◽

10.1182/blood-2021-146381 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2573-2573

Author(s):

Giovanni Caocci ◽

Olga Mulas ◽

Daniela Mantovani ◽

Alessandro Costa ◽

Andrea Galizia ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Present Report ◽

Univariate Analysis ◽

Vaccine Dose ◽

Humoral Response ◽

The Other ◽

World Health ◽

International Prognostic Scoring System ◽

Humoral Immune

Abstract Introduction. Patients with Myelofibrosis (MF) are considered fragile and thus eligible in Italy for COVID-19 BNT162b2 mRNA vaccination. According to the International Prognostic Scoring System (IPSS), patients with intermediate and high MF, may receive clinical benefits from ruxolitinib, the first approved JAK1/JAK2 inhibitor. Given the potent anti-inflammatory properties of ruxolitinib against immunocompetent cells, we previously reported a lower but non-statistically absolute IgG anti-Spike humoral response in vaccinated MF patients treated with ruxolitinib. In the present report we extended the cohort of MF patients. Methods. All MF patients received 2 injections of 30 ug per dose of BNT162b2 mRNA COVID-19 vaccine 3 weeks apart, according to the standard protocol. After injection, mild pain at the injection site was frequently reported. No serious adverse events were registered. The serum level of IgG anti-Spike glycoprotein was tested after a median time of 45 days (range 40-60) from the second vaccine dose, using the approved anti-SARS-CoV-2 IgG CLIA (LIAISON® SARS-CoV-2 TrimericS IgG assay, Diasorin, Saluggia, Italy). An Arbitrary Units per milliliter (AU/mL) ratio of <12.0 was considered to be negative, 12.0-15.0 AU/mL to be borderline and >15 AU/mL to be positive. A conversion of AU/mL to binding antibody units (BAU/mL) as recommended by the World Health Organization (WHO) guidelines was achieved considering the following equation: BAU/mL = 2.6*AU/mL. Results. Overall, 30 MF patients (median age 65 years, range 48-83) were vaccinated. A diagnosis of primary MF was reported in 21 cases (70%), post essential thrombocythemia-MF in 6 (20%) patients and post polycythemia vera-MF in 3 (10%) patients; 23 out of 30 patients (76.6%) were positive for the JAK2V617F, 5 (16.6%) for CALR mutation, 1 (3.3%) for MPL mutation and 1 patient (3.3%) resulted triple negative. Splenomegaly was observed in 14 patients (46%) and 19 (63.3%) reported comorbidities. Nineteen patients (63.3%) were classified as DIPSS low or intermediate-1 risk, and 11 (36.6%) as intermediate-2 or high risk. Fifteen patients (50%) were receiving ruxolitinib, at a median total dose of 20 mg/die (range 20-40 mg) and the remaining 15 patients other treatments (8 patients hydroxyurea and 7 only supportive therapy). None of the patients reported COVID-19 infection neither previous nor subsequently to vaccination. Overall, a positive immune response against COVID-19 was observed in 8 out of 15 patients (53.3%) in the ruxolitinib group, in comparison with 13 out 15 patients (86.6%) in the other treatment group (p=0,046). The absolute IgG anti-Spike value was lower in the ruxolitinib group (median 35.2±49.81) in comparison with the other group (median 226.1±163.9; p=<0.001), Figure 1. In univariate analysis, only ruxolitinib treatment was found associated with a lower humoral immune response to the vaccine. Conclusions. MF patients under ruxolitinib achieved a lower humoral immune response in comparison with MF patients who underwent other treatments. No COVID-19 infection was observed in both groups after vaccination, after a median follow up of 3 months since the second dose. Whether patients with a potential insufficient humoral response to vaccine will benefit from a third dose of BNT162b2 mRNA COVID-19 vaccine is a matter of further investigation. Our preliminary data need to be confirmed in larger cohort of MF patients. Figure 1 Figure 1. Disclosures Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria.

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Anti-Inflammatory Activities of Captopril and Diuretics on Macrophage Activity in Mouse Humoral Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms222111374 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11374

Author(s):

Paweł Bryniarski ◽

Katarzyna Nazimek ◽

Janusz Marcinkiewicz

Keyword(s):

Immune Response ◽

B Cells ◽

Humoral Immune Response ◽

Humoral Response ◽

Peritoneal Macrophages ◽

Surface Markers ◽

Immunomodulatory Effects ◽

Humoral Immune ◽

Macrophage Activity ◽

Anti Inflammatory

Hypertension is accompanied by the over-activation of macrophages. Diuretics administered alone or in combination with hypotensive drugs may have immunomodulatory effects. Thus, the influence of tested drugs on mouse macrophage-mediated humoral immunity was investigated. Mice were treated intraperitoneally with captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) by 8 days. Mineral oil-induced peritoneal macrophages were harvested to assess the generation of cytokines in ELISA, and the expression of surface markers was analyzed cytometrically. Macrophages were also pulsed with sheep red blood cells (SRBC) and transferred to naive mice for evaluation of their ability to induce a humoral immune response. Tested drugs increase the expression of surface markers important for the antigen phagocytosis and presentation. SRBC-pulsed macrophages from mice treated with captopril combined with diuretics increased the secretion of antigen-specific antibodies by recipient B cells, while macrophages of mice treated with hydrochlorothiazide or furosemide with captopril increased the number of antigen-specific B cells. Tested drugs alter the macrophage secretory profile in favor of anti-inflammatory cytokines. Our results showed that diuretics with or without captopril modulate the humoral response by affecting the function of macrophages, which has significant translational potential in assessing the safety of antihypertensive therapy.

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Antibody response after COVID-19 mRNA vaccination in relation to age, sex, and side effects

10.1101/2021.04.19.21255714 ◽

2021 ◽

Author(s):

Paul Naaber ◽

Virge Jürjenson ◽

Ainika Adamson ◽

Epp Sepp ◽

Liina Tserel ◽

...

Keyword(s):

Immune Response ◽

Side Effects ◽

Immune Responses ◽

Antibody Response ◽

Older Individuals ◽

High Efficacy ◽

Vaccine Response ◽

Antibody Levels ◽

The Impact ◽

Older Males

AbstractBackgroundThe mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses.MethodsWe here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations.FindingsOur findings show a robust immune response to the Spike protein’s RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose.InterpretationThe Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine.FundingThe study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.Research in contextEvidence before this studyThe first studies addressing the immune responses in older individuals after the single-dose administration of the SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms “SARS-CoV-2”, “COVID-19”, “vaccine response”, “mRNA vaccine”, up to April 15th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the role of age, sex and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within 1-2 weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Even less information is available on sex differences or correlations with mRNA vaccine side effects.Added value of this studyIn this study, we assessed the antibody response up to 6 weeks after the second dose of Pfizer-BioNTech Comirnaty mRNA vaccine in 118 individuals. Our findings show a strong initial immune response after the first dose and an even higher Spike RBD antibody levels at 1 week after the second dose, but these significantly declined at 6 weeks after the second dose. We also found a weaker immune response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Furthermore, although overall female and male vaccinees responded similarly, we found that age-related waning of the vaccine-related antibodies was stronger amongst older males whereas in females the impact of age was lost at 6 weeks after the second dose.Implications of all the available evidenceNew mRNA vaccines are now applied worldwide as they have shown high efficacy in clinical trials. Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody response to Spike RBD region but these high levels decline 1.5 months after the second dose in most of the vaccinated individuals. Nevertheless, even at 6 weeks after the second dose, they stay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. These findings also implicate that fewer adverse effects may indicate lower antibody response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.

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Systemic COVID-19 vaccination also enhances the humoral immune response after SARS CoV-2 infection in the population of an oncology hospital in Poland. Criteria for COVID-19 re-immunization are needed.

10.21203/rs.3.rs-858160/v4 ◽

2021 ◽

Author(s):

Piotr Kosiorek ◽

Dorota Kazberuk ◽

Anna Hryniewicz ◽

Robert Milewski ◽

Samuel Stróż ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Post Infection ◽

Half Life ◽

Humoral Response ◽

Control Group ◽

Igg Antibodies ◽

Hospital Laboratory ◽

Humoral Immune ◽

Chemiluminescent Immunoassay

Abstract Systemic vaccination of the BNT162b2 mRNA stimulates humoral response. Our study aimed to compare the intensity of humoral immune response, measured by SARS CoV-2 IgG, SARS CoV-2 IgM, and neutralization S-RBD IgG antibodies level, post COVID-19 vaccination versus post-SARS COV-2 infection. We analysed 1060 people in the following groups: convalescents, healthy vaccinated, vaccinated with COMIRNATY, AstraZeneca, Moderna, Johnson & Johnson, and vaccinated SARS CoV-2 convalescents. A concentration of SARS CoV-2 IgG, SARS CoV-2 IgM, and neutralizing S-RBD IgG was estimated in hospital laboratory by chemiluminescent immunoassay - CLIA, MAGLUMI. Results: 1. We observed a rise of antibodies response in both convalescent SARS CoV-2 and COVID-19 vaccinated groups 2. The level of all antibodies’ concentrations in vaccinated COVID-19 convalescents was significantly higher. 3. We differentiated asymptomatic SARS CoV-2 convalescents from the control group. Based on our analysis, we suggest that it is essential to monitor SARS CoV-2 antibodies concentrations as an indicator of asymptomatic COVID-19 infection and equivalent to the effectiveness of humoral response in convalescents and vaccinated people. Considering the time-limited nature of the effects of post-infection SARS CoV-2 recovery or vaccination, among others physiological half-life, we suggested monitoring IgG antibodies level as a criterium for the next vaccination.

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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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