kynurenine pathway and Sjogren's syndrome

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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
 
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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.
 
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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.