kynurenine pathway and Sjogren's syndrome

pattismith

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Neurological and Inflammatory Manifestations in Sjögren’s Syndrome: The Role of the Kynurenine Metabolic Pathway
2018

Abstract
For decades, neurological, psychological, and cognitive alterations, as well as other glandular manifestations (EGM), have been described and are being considered to be part of Sjögren’s syndrome (SS).

Dry eye and dry mouth are major findings in SS. The lacrimal glands (LG), ocular surface (OS), and salivary glands (SG) are linked to the central nervous system (CNS) at the brainstem and hippocampus.

Once compromised, these CNS sites may be responsible for autonomic and functional disturbances that are related to major and EGM in SS.

Recent studies have confirmed that the kynurenine metabolic pathway (KP) can be stimulated by interferon-γ (IFN-γ) and other cytokines, activating indoleamine 2,3-dioxygenase (IDO) in SS.

This pathway interferes with serotonergic and glutamatergic neurotransmission, mostly in the hippocampus and other structures of the CNS.

Therefore, it is plausible that KP induces neurological manifestations and contributes to the discrepancy between symptoms and signs, including manifestations of hyperalgesia and depression in SS patients with weaker signs of sicca, for example.

Observations from clinical studies in acquired immune deficiency syndrome (AIDS), graft-versus-host disease, and lupus, as well as from experimental studies, support this hypothesis. However, the obtained results for SS are controversial, as discussed in this study.
Therapeutic strategies have been reexamined and new options designed and tested to regulate the KP. In the future, the confirmation and application of this concept may help to elucidate the mosaic of SS manifestations.
 
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Very very interesting paper. Ties in many symptoms & markers a subset of ME patients are starting to report, but in Sjogrens. Very interesting how it describes the progression of CNS dysfunction in a disease many think is just dry eyes and month. Even mentions antibodies to Muscarinic receptors that recent ME research is also highlighting (Cell Trend test).

This is one I'm going to read a few times. Thanks for posting @pattismith
 

Belbyr

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Therapeutic strategies have been reexamined and new options designed and tested to regulate the KP. In the future, the confirmation and application of this concept may help to elucidate the mosaic of SS manifestations.

Wonder what they are doing with this...?
 
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Therapeutic strategies have been reexamined and new options designed and tested to regulate the KP. In the future, the confirmation and application of this concept may help to elucidate the mosaic of SS manifestations.

Wonder what they are doing with this...?
Section 6 of the paper linked describes therapies to modulate the KP - however you have to follow all the references (I didn't do this) and the text in section 6 is rather vague.

I did come across this paper recently. Unfortunately the text of the paper is not available without paying.
Intravenous Immunoglobulin Therapy in Refractory Autoimmune Dysautonomias: A Retrospective Analysis of 38 Patients (Jill Schofield May2018).

CONCLUSIONS:
There is increasing evidence that IVIG is safe and effective in a subset of patients with autonomic disorders and evidence for autoimmunity. A 4-month IVIG trial should be considered in severely affected patients who are refractory to lifestyle and pharmacological therapies. Antiphospholipid antibodies and novel Sjögren antibodies are often present in these patients and correlate with a high response rate to IVIG.
 

pattismith

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Belbyr

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I never really have dry mouth, sometimes the opposite. I do get bad dry lips (but I have big lips) and I do have eye symptoms like floaters, pressure, and seeing visual snow in daytime and nighttime. I've been tested for Sjogrens but never had a lip biopsy or tested for the 'early' antibodies. Skin punch biopsies of my leg were normal.
 

Belbyr

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I wish we could hear how Whitney is doing on IVIG from his mother or father, I think he has been on it for at least a few months by now, maybe?
 

pattismith

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I wish we could hear how Whitney is doing on IVIG from his mother or father, I think he has been on it for at least a few months by now, maybe?
According to the news Janet is giving regularly, Whitney didn't improve from IVIG
 

Sing

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I am so sorry that it hasn’t worked for Whitney! He has suffered so much.

I also wanted to say that I am in the Sjogren’s/autoimmune subset and my doctor is going to try to get me access to IVIG at the higher dosage effective to overwhelm the autoantibodies. But this is more expensive than even the dosage required to treat the low immune levels I also have, and he says that Medicare is harder than most forms of insurance here to get it paid for. If not this, then Rituximab—my last option, I gather.

What I wish is that effective treatments be devised and available to all of us, much sooner after a seriously down-regulated system and autoimmune illness are identified, rather than the 22 years in my case. Maybe then, the opportunities for further complications would not have the many chances to arise that they have now.

I also wish that soon after onset, more rest was insisted upon by doctors and supported also in terms of insurance/disability—though I can’t see that happening in the U.S. But at least if doctors insisted upon it, more patients might get more family support to do this. Long term resting is something our world now denies value to, even though it used to be considered necessary, essential, in the past with many conditions. It might help a lot more patients move past the worst period of exposed vulnerability, and a lot of these “plot developments” would not be happening with the fervor and tenacity they have.
 

Sing

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The idea isn’t to lower immunity, which a lot of us are already deficient in, but to wipe out the memory, at least for a time, of our immune systems so that they don’t keep going on attacking and reacting to the same old stuff or in the same old ways.. Our own immune systems could be sabotaging our health in particular ways, so a drug like Rituximab depletes its memory for a time, so there can hopefully be a reset. This seems to help some people with ME/CFS—a couple of researchers have suggested about one third—but it looks as though the majority is not helped, so it has lost its place as a promising candidate for an official/approved treatment. If you are in the one third who can benefit, however, it might really do so.