Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD)

[pattismith]

The authors seem to consider that seronegative autoimmune disorders are simply distinct autoimmune disease that doen't have any name yet because the lack of specific identified AAb .
My guess is that Fibro or ME/CFS may have subset in this category.

Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD)

J. N. Pouw E. F. A. Leijten J. M. van Laar M. Boes

First published: 22 October 2020

https://doi.org/10.1111/cei.13542

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Summary

Autoimmune rheumatic diseases (AIRD) are categorized seropositive or seronegative, dependent upon the presence or absence of specific autoreactive antibodies, including rheumatoid factor and anti‐citrullinated protein antibodies.

Autoantibody‐based diagnostics have proved helpful in patient care, not only for diagnosis but also for monitoring of disease activity and prediction of therapy responsiveness.

Recent work demonstrates that AIRD patients develop autoantibodies beyond those contained in the original categorization.

In this study we discuss key mechanisms that underlie autoantibody development in AIRD: defects in early B cell development, genetic variants involved in regulating B cell and T cell tolerance, environmental triggers and antigen modification.

We describe how autoantibodies can directly contribute to AIRD pathogenesis through innate and adaptive immune mechanisms, eventually culminating in systemic inflammation and localized tissue damage.

We conclude by discussing recent insights that suggest distinct AIRD have incorrectly been denominated seronegative

 

[nerd]

How average physicians see it: "seronegative" => psychosomatic hypochondriac, possibly with anxiety disorder or depression

 

[Pyrrhus]

The authors seem to consider that seronegative autoimmune disorders are simply distinct autoimmune disease that doen't have any name yet because if the lack of specific identified AAb .

Thanks @pattismith for sharing this paper.
I especially liked the summary of known pathways leading to loss of B cell tolerance.

But the first paragraph in the introduction has triggered me:

Autoimmune rheumatic diseases (AIRD) are heterogeneous musculoskeletal disorders accompanied by substantial morbidity and mortality. AIRD mainly, although not exclusively, affect joints and muscles and are characterized by the presence of specific autoantibodies [1]. Traditionally, AIRD are classified as ‘seropositive’ or ‘seronegative’, according to whether or not autoantibodies are a known important feature [2]. Examples of seropositive AIRD include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (pSS) and idiopathic inflammatory myopathies (IIM) [3]. Importantly, although RA is classified within the seropositive category, approximately 30% of patients lack the presence of the classic autoantibodies rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) and have ‘seronegative RA’ [4].

"seronegative autoimmune". Sigh.

I would again like to point out that if there are no auto-antibodies nor auto-reactive T cells, then a doctor can't call it autoimmune.

Of course, there may be unidentified auto-antibodies or unidentified auto-reactive T cells. This is perfectly plausible. But a doctor still can't declare it autoimmune until such auto-reactivity is identified. Until then, the only honest adjective one can use is "idiopathic".

Another example of doctors using the word "autoimmune" when they really mean "idiopathic"...

Sigh.

 

[pattismith]

@Pyrrhus

so if you call them idiopathic rheumatic diseases, you can't use immunosuppressant drugs to treat them (because they are not auto-immune so not likely to respond to it)?

 

[Pyrrhus]

@Pyrrhus

so if you call them idiopathic rheumatic diseases, you can't use immunosuppressant drugs to treat them (because they are not auto-immune so not likely to respond to it)?

"Idiopathic" simply means "we don't know the cause."
If it's idiopathic, it could eventually turn out to be auto-immune, viral, both, or something else altogether.

Immunosuppressant drugs are used in lots of idiopathic conditions.

Hope this clarifies.

 

[pattismith]

"Idiopathic" simply means "we don't know the cause."
If it's idiopathic, it could eventually turn out to be auto-immune, viral, both, or something else altogether.

Immunosuppressant drugs are used in lots of idiopathic conditions.

Hope this clarifies.

don't you think that if an immunosuppressant drug works for a disease, it is more likely auto-immune than infectious?

 

[nerd]

don't you think that if an immunosuppressant drug works for a disease, it is more likely auto-immune than infectious?

I think immune dysregulation is the fitting term if you speculate about a viral background. Immune dysregulation can lead to autoimmunity, but you don't need autoimmunity to experience the effects of immune dysregulation. Immune-suppressive/Anti-inflammatory treatment has shown to be very helpful with COVID-19's immune dysregulation, but it's unclear if it resolves the causal pathology and not just some of the severe effects. Long haulers basically suffer from immune dysregulation. Will anti-inflammatory treatment help them? Still unclear...

 

[Pyrrhus]

don't you think that if an immunosuppressant drug works for a disease, it is more likely auto-immune than infectious?

Not necessarily.
If an immunosuppressant drug works for a condition, then it's probably inflammatory.

But inflammation can be caused by many things. Auto-reactivity is only one possibility.

Hope this helps.