Hi - I've been reading medical research on Sjogren's for the past 2.5 years to help my wife who has salivary gland destruction, neuropathic pain, RF+, SSA and SSB presenting, etc.

 

I think MMP9 is the link between the pathologies, and I believe MMP9 dysregulation can be accomplished by a variety of pathogens, injuries and possibly drugs, and is the cornerstone of Sjogren's dysregulation. https://www.ncbi.nlm.nih.gov/pubmed/28818099 (among many others, and all links hereafter just to illustrate the point, not be a definitive study - I'm not going to footnote every article that got me here).

I don't believe MMP9 causes RA, Atherosclerosis or Depression, but it may be what activates these diseases for Sjogren's patients (i.e. a variety of causes for those diseases). I believe MMP9 starts the inflammatory cascade that results in the substantial dysregulation of the immune system (increased IL-6, increased CRP, increased BAFF, increased CXCL5, b12 deficiency, decreased Mucin production, etc) which result in salivary and acinar glad destruction.

 

The main phenotype for Sjogren's is post-menopausal women; I propose for this cohort it is Estrogen reduction that results in persistent MMP9 elevation, as Estrogen represses MMP9 activation.https://www.ncbi.nlm.nih.gov/pubmed/19668239 Vitamin D deficiency also elevates MMP9 https://www.ncbi.nlm.nih.gov/pubmed/12454321 so Vitamin D-deficient, post-menopausal women might be doubling-down. A high-fat diet also increases MMP9 https://www.ncbi.nlm.nih.gov/pubmed/24935427 so it could be that any combination that brings MMP9 levels above a critical point induces the persistent dysregulation found in Sjogren's. All 3 combined would be fairly common among American women.

 

In my wife's case, she is Vitamin D deficient but not post-menopausal; she only has oral mucosal involvement with no ocular presentation really. Enamel defects that leave her susceptible to cavities and periodontitis; for her I propose P. Gingivalis which upregulates and cleaves MMP9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939075/. P. Gingivalis also rewires Toll-Like Receptor responses, leading to neutrophils stuck in an inflammatory state: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071223/, and P. Gingivalis neutrophils are impervious to IL-10 induced apoptosis, allowing them to survive longer: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC308905/pdf/0650.pdf In addition, P. Gingivalis-primed macrophages promote Tolerance mechanism, unlike naive or tnf-a co-stimulated: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158629

 

 

For non-post-menopausal, with involvement in ocular (and/or oral presentation) I propose HSV1 https://www.ncbi.nlm.nih.gov/pubmed/12873454 or P. Aeruginosa https://www.ncbi.nlm.nih.gov/pubmed/16384971 and I assume there are more.  

 

I'd be very curious to hear from any researchers or doctors out there.

We've found DHA Extra Nordic Natural fish oil has helped here (1-2g/day for dryness) and Berberine (gastric motility, mood, fatigue issues, as Berberine inhibits MMP9), and she takes Plaquinil and 5mg Prednisone daily for disease maintenance.