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Juvenile inflammatory rheumatic disease associated with a higher antibody response to seasonal coronavirus

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen behind the current epidemic of coronavirus disease 2019 (COVID-19) is the beta coronavirus family of coronaviruses. However, there are other human seasonal coronaviruses that cause human infection with endemic disease, with mild common cold symptoms. SARS-CoV-2 infections range from mild symptoms such as runny nose, stuffy nose, and mild fever to severe gastrointestinal and respiratory illnesses and can end with multiple organ failure.

SARS-CoV-2 vs. HCoV-OC43 infection

Complications of COVID-19 are observed in less than one-tenth of patients and include risk factors such as male gender, age, ethnic background, lack of access to medical care, and pre-existing conditions. The majority of infections are asymptomatic.

Children are more likely to be asymptomatic. In contrast, they are at increased risk of carrying one of the seasonal human coronaviruses (HCoVs) and are more likely to have existing antibodies and memory B cells.

Children have also been found to develop multi-organ inflammatory syndrome (MIS), which is thought to be a poorly understood inflammatory complication, reflecting dysregulation of the antibody response after COVID-19. I will.

Risk of COVID-19 in juvenile inflammatory conditions

Children with inflammatory rheumatoid disorders such as juvenile idiopathic arthritis (JIA), juvenile dermatomyitis (JDM), and juvenile systemic lupus erythematosus (JSLE) have uncontrolled antibodies and inflammatory responses, resulting in COVID- 19 were considered high risk. As a fact that they were often receiving immunosuppressive treatment. However, there was a lack of specific information.

New research released in bioRxiv* The server compared the antibodies produced in young patients in these three states with the two immune-dominant coronavirus antigens, spike and nucleocapsid antigens. Researchers have chosen to study patients infected with HCoV-OC43, one of the seasonal HCoVs. This is very common in this group and SARS-CoV-2 infection is rare due to the shield.

The underlying premise is that HCoV-OC43 can induce not only antibodies specific for that antigen, but also cross-reactive antibodies to SARS-CoV-2. This study is generally aimed at understanding this antibody response as a substitute for a humoral response to coronavirus infection.

The SARS-CoV-2 virus, which is currently prevalent, is thought to be as likely to be endemic as the current HCoV. In fact, HCoV-OC43 has a history of mutations, suggesting that it has recently jumped over species barriers to infect humans. If so, it indicates that the virus may have caused the first pandemic.

For this reason, current studies may help clarify the response to SARS-CoV-2, even if it becomes endemic.

Antigen-antibody reaction to HCoV-OC43 spike

This study shows that IgG is the primary antibody response to the spike antigen and constitutes approximately 70% and 60% of all antibodies to HCoV-OC43 and SARS-CoV-2, respectively. The rest consisted of IgM antibodies, with the lowest amount of IgA.

Most healthy children and adolescents had IgG for HCoV-OC43 spikes, but the proportion of detectable SARS-CoV-2 spike antibodies was small and the titers were much lower. The same profile was seen in patients with JIA, JDM, and JSLE.

However, the proportion of JDM and JSLE patients with IgG to HCoV-OC43 spikes was much higher than the control. Patients with JSLE also had a higher prevalence of IgG for SARS-CoV-2 spikes compared to healthy controls.

After classifying JSLE into ages 1-12 and 13-18, researchers found that younger patients with JIA and JDM had higher anti-HCoV-OC43 spike IgG than controls with older patients. Did. Patients with JSLE were usually older than pediatric patients with the other two conditions, but their total and IgG anti-HCoV-OC43 spike antibodies were also higher.

IgA anti-HCoV-OC43 spike antibody was increased in all JSLE and elderly JIA patients.

Antibodies to SARS-CoV-2 spikes

Although the titer was low and the correlation with HCoV-OC43 spike antibody was low, all three classes of patients showed antibody against SARS-CoV-2 spike. Patients with JSLE and younger patients with JIA showed higher IgG titers for SARS-CoV-2 spikes. Elderly JIA patients showed below average anti-SARS-CoV-2 antibody titers.

After adjusting for female gender, age, steroid use, and year of collection, HCoV-OC43 spike antibodies were even higher in JSLE patients and IgGHCoV-OC43 spikes were higher in younger patients with one of three conditions.

Women and women taking steroids had higher antibody titers. Steroid use may indicate a more serious rheumatoid disease, but it may also indicate immunodysregulation, especially in patients with JSLE.

After adjusting for confounding factors, total antibody against SARS-CoV-2 spikes was low in JDM, but IgG levels were high in JSLE patients.Both total antibody and IgGSARS-CoV-2 spike antibody with young patients Autoantibodies..

Association with autoantibodies

The association between SARS-CoV-2 spikes and HCoV-OC43 spike antibodies in the presence of autoantibodies is comparable between these spike antibodies and antibodies against HERV-encoded envelope glycoproteins (also essentially autoantibodies). This is important when there is an association of. Take into account. This may indicate that high spike antibody levels in these patients reflect the underlying overactivity of adaptive immunity.

Neutralization titers were similar under all three conditions when evaluated on most sera using cross-reactive SARS-CoV-2 IgG. Neutralizing ability was weakly associated with antibodies to SARS-CoV-2 spikes, but not with IgG against HCoV-OC43 spikes.

“”Our findings suggest that inflammatory rheumatoid disease does not interfere with, or even enhances, humoral immunity to seasonal HCoV in this age group... “

Coronavirus nuclear protein primarily stimulates the IgM response

Younger patients with any of these conditions showed higher IgG responses Spike protein, This may be the result of an exaggerated immune response or increased viral load due to immunosuppressive therapy.To investigate this, researchers measured antibodies to a nuclear protein (N) that normally does not produce. Neutralizing antibody.. Therefore, this will provide a clearer idea of ​​virus replication.

They found that most anti-N antibodies belong to the IgM subclass and account for 82% and 67% of all antibodies against the HCoV-OC43 and SARS-CoV-2 N proteins, respectively. In contrast, healthy adult controls produced both IgG (30%) and IgM (62%) antibodies against the HCoV-OC43 N protein.

Conversely, healthy pediatric controls produced only 9% IgG relative to the HCoV-OC43 N protein, but 85% IgM. This indicates that the coronavirus N protein stimulates the predominant response of IgM by slowing the class switch to IgG with age.

In young patients with JDM and JIA, both total and IgM antibodies to the N protein were reduced.

These findings show differences in antibody response in young patients exposed to coronavirus spikes and N protein. The two are not strongly correlated. This can mean that either may be the immune predominance of the individual patient.

However, in all disease groups, spike antibodies were higher than N antibodies, regardless of the virus tested (HCoV-OC43 or SARS-CoV-2). This was more likely with women and steroid treatment, but less with old age. This indicates less exposure to the virus and a lower risk of adverse consequences.

What is the impact?

This study examines the differences in antibody responses to coronavirus in adults and children and the effects of underlying immunosuppression. Researchers have found that in young patients with JIA, JDM, and JSLE, the antibody response is equal to or stronger than that of healthy controls.

IgG was predominant in the HCoV-OC43 spike, but there was also cross-reactive IgG to SARS-CoV-2. However, antibody production against these two viral nucleoproteins showed a slow class switch that occurred with age and did not rise from baseline in patients with these conditions.

This indicates that the reason for the high antibody response in these patients was not increased exposure. The result was a favorable ratio of spikes to nucleoprotein antibodies.

The data suggest children and adolescents if the response to SARS-CoV-2 or vaccination can be inferred from the response to HCoV-OC-43, along with the presence of existing cross-reactive antibodies to SARS-CoV-2. Patients with the most common inflammatory rheumatic diseases begin a highly effective humoral response to SARS-CoV-2 infection or vaccination. “

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.

Juvenile inflammatory rheumatic disease associated with a higher antibody response to seasonal coronavirus

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