Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis, 2023, OLIVIA G. THOMAS et al

Abstract
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con).

Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4+ T cell responses were detected in natalizumab-treated pwMS.

This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development.

https://www.science.org/doi/10.1126/sciadv.adg3032

 

Common viral antibodies could trigger MS, research reveals

“We have discovered that certain antibodies against the Epstein-Barr virus which would normally fight the infection can mistakenly target the brain and spinal cord and cause damage.”
...
"EBV is one of the most widespread viruses in humans. More than 90% of the world’s population are infected and most people only experience mild cold symptoms. After infection, the virus sits dormant in the body, kept suppressed by antibodies.

However, the latest work suggests that, in some people, these antibodies could be involved in triggering MS.

They found that antibodies that bind to a certain protein in the Epstein-Barr virus, EBNA1, can also bind to a very similar-looking protein in the brain and spinal cord called CRYAB, which plays a crucial role in protecting against the effects of inflammation.

If antibodies are mopping up CRYAB, this could result in damage to the nervous system and contribute to severe symptoms in MS patients, including problems with balance, mobility and fatigue."

https://www.theguardian.com/society...-antibodies-could-trigger-ms-research-reveals

 

Can homology be a good explanation for autoimmunity? Seems fitting. An immune response creates antigens that interfere with other proteins/molecules because they fit in the same receptors. Especially if B cells stick around and continue releasing the antigens. Or if a pathogen remains present, keeps causing an immune response.

Autoimmunity always seems to have that magical element of "something occurred" but it has to start somewhere and this makes a lot of sense. To hear some people promoting rampant infections, they think the immune system is perfect and never makes mistakes (half of every human ever born is not available to comment, died in childhood of common infections). But it's a kludge of a process rife with errors. And it works by, you know, killing individuals over time.

In the end proteins are basically electrochemical programs. The same program can be written different ways.