Hi All,
New to posting. Long time lurker. I have a ton of questions, but wanted to start with my most pressing; I've seen conflicting reports on Sjogren's being a TH1 versus TH2 dominant condition. I'm seeing my Rheumatologist on Friday and want her to run some additional testing, I'm trying to get a basic understanding of immunology, as I don't present as a typical soggie.
Thanks!!! Looking forward to chatting with you all!!!
Generally Sjogren's is considered Th1 dominant on it's own, but depending on accompanying diseases, there can be a balance of T helper cells, or it can lean to Th2 dominance depending on the secondary disease (lupus, for example is Th2 dominant, and can result in balancing the Th cells so there is no dominance).
Having had Sarcoidosis for nearly 40 years, and very Th1 dominant, I've always tried to maintain balance with various Th2 stimulators like caffiene, green tea and turmeric. I do notice that if exposed to Th1 sitmulants, like echinacea, Vitamin C, or ginsing, I go into flare.
I have also always been very aware of Vitamin D levels, and have taken at least 2000 IU daily since long before it was fashionable, and it is now being proclaimed T-regulatory supporting compound.
My personal experience has had less to do with which T helper cells are elevated, and more to do with maintaining a balance between the two (actually three since neutral Th0 are occasionally mentioned) even if both tend to be elevated.
This is information I am curious about. I am currently in a bad flare with neuropathy and this all started last summer with high homocysteine and HRCRP levels that the doctors weren't concerned about. It was allowed to continue until the day hit in January that I had all the symptoms of histamine intolerance and by eating low histamine I was able to get some of the awful pain on my face to calm down. How do I know what I am and could that be pushing this flare? When I have vitamin c, be it ascorbic acid or citric acid my ears ring in a big, big way. What do I ask the doctors to test for that they won't look at me like I am crazy? Thanks, a good question.
Hello,
Here is an article/abstract I found in researching this:
http://www.ncbi.nlm.nih.gov/pubmed/9200929
Cheers...
Great article, SJSman, and it seems to address something I had wondered about because they find differences in Th cell balances between "organ specific" and "systemic" autoimmune disease. I wonder if that could be why my text stated Sjogren's as Th1, possibly dealing with primary, non-systemic Sjogren's only?
This could also lead to the rapidly shifting imbalances ( my immunologist calls it "cycling") prevalent in multiple AI diagnoses: the onset of an organ specific disease stimulates Th1 production, while the ongoing diagnoses have already stimulated Th2 production, causing a shift in predominance. Time for a visit with my friends in the research immunology department!
I have found that the more recent studies and articles differ in their findings and opinions from the older articles. The first article is very detailed and offes a plethora of information about the immune dysfunction of Sjogren's. I have copied and pasted only a tiny portion of the article. The full article is well worth reading.
From Journal of Immunology Research
The Immune Factors Involved in the Pathogenesis, Diagnosis, and Treatment of Sjogren's Syndrome
"3.1. Th1 and Th2 Cells
Traditional opinion about these two Th subsets is that there is a dynamic balance between the two families of cytokines; while uncontrolled Th1 cells determine autoimmune states, unusual deviation to Th2 cells leads to allergic disorders [15]. The observation of Fox and Kang that increased levels of IL-1b, IL-6, tumor necrosis factor (TNF)- , and IFN- have been reported in saliva from patients with SS in comparison with controls with histologically normal salivary glands, suggests that Th1 responses predominate in SS autoimmune lesions [16]. In some autoimmune cases, however, reduction of the Th1 response or a Th2 type shift may alleviate disease; many apparent exceptions are now well documented. And Th2-derived cytokines such as IL-10 have been found to be elevated in the saliva of Sjogren?s syndrome patients and correlate with the severity of the disease [17]. The results of Mitsias and his colleagues reported that Type II microenvironment prevails in low-grade infiltration, while type I pattern increases in patients with definite SS, and patients with advanced lymphocytic infiltration may suggest that the cytokine pattern may shift from Th1 to Th2 as the immunopathological lesions progress [18]. Detailed mechanism of how steroid hormone and cytokines regulate the Th1/Th2 is a complex issue that needs more research, and, hopefully, some new treatment options may be drawn from this.
3.2. Th17 and Tregs
In spite of the role of Th1 and Th2 cells in sjogren?s syndrome which remains contradictory, several data show that some abnormalities that first ascribed to Th1 cells were instead engendered by Th17 cells [19]. Th17 cells produce a family of cytokines from IL-17A through IL-17F, and, to a lesser extent, TNF-α and IL-22, which have been detected in the serum and saliva of SS patients, and IL-17 expression correlated with the severity of lesions. On the other hand, Tregs are thought to exert a countervailing suppressive effect on Th17 mediated cellular immunity. The reports are contradictory in that the blood of SS patients contains too many or too few Treg cells. Nguyen et al. [20] and Cornec et al. [21] found that the Th17/IL-23 system is upregulated in C57BL/6.NOD-Aec1Aec2 mice and SS patients at the time of disease and proposed the hypothesis that in the presence of IL-6, the T-cell differentiation might switch from Treg-cell pathway to Th17 pathway. As well as rheumatoid and systemic lupus erythematosus, shown by earlier investigations, IL-6 has been detected in the salivary glands of patients with SS, which not only participates in the generation of Th17 but also fosters their proliferation. IL-18, TGF- , and other cytokines participate in the regulation of T cells in a complicated way, and more investigations are needed to be clarified."
http://www.hindawi.com/journals/jir/2013/160491/
Another article:
http://www.medscape.com/medline/abstract/16166103
And this is another article with much detail but it is an older article. Again, I copied and pasted only a very small part of this article. The full article is worth reading. However, the Hindawi article (above) is a much more recent article.
From Wiley Online Library:
The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren?s syndrome
"Our findings showing that type-1 and type-2 cytokines do not demonstrate a restricted profile in LSG of SS patients are not surprising. Numerous studies have provided evidence indicating that human T helper cells present a less polarized profile than their mouse counterparts and that Th1 and Th2 cells are still able to produce IL-4 and IFN-γ, respectively [34?36]. Thus current understanding supports the idea that immune responses are influenced mainly by the balance between types-1 and -2 cytokines. The novel finding and of biological significance in our studies is that, depending on the grade of infiltration and the clinical status of the patients, the balance of Th1/Th2 cytokines changes in favour of Th1 cytokines in late lesions. The functional prevalence of Th2 cytokines in early lesions is characterized by IgE production in vitro. It is noteworthy that this IgE production probably reflects an in vivo phenomenon, as in vitro switching to IgE is unlikely to take place as early as 6 days of culture [37,38]. All the above support the hypothesis advanced by Ferracioli and De Vita [39].
The prevalence of type-2 cytokines in early lesions in SS, a systemic autoimmune disease, may be of more general significance and is consistent with recent studies showing that: (1) large numbers of low-affinity autoreactive T cells escape clonal deletion and are present in the periphery of normal animals [40] and (2) after antigenic stimulation, T cells bearing low affinity T cell receptor (TCR) preferentially express type-2 cytokines [41,42]. Based on these reports, a probable hypothesis explaining the prevalence of type-2 cytokines in early SS is that low affinity autoreactive T cells are recruited and activated (for unknown reasons) in the salivary glands at the initiation of the autoimmune reaction. Because these cells bear low-affinity TCR, they would express a type-2-biased cytokine profile, which is consistent with our results. The skewing of the cytokine profile during the progress of the disease may result from the accumulated changes in the microenvironment of the lesion, including fibrosis or other tissue components [43], and locally produced chemokines that may also contribute to the redirection from a typ-2 to a type-1 immune response.
In summary, in this study we provide evidence suggesting that in SS type-1 and type-2 cytokines are in dynamic balance. Type II microenvironment prevails in low-grade infiltration, while type I pattern increases in patients with definite SS and patients with advanced lymphocytic infiltration."
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2249.2002.01869.x/full
Thank you for this topic Gosford. Does anybody else ever get angry that they are doing so little about this disease in terms or really good treatments? There should be some good biologics for us. I worked in the field of immunology for years and it just really ticks me off. But, if they know which cells and chemicals are out of balance, there might be a good treatment on the way. I wonder if our doctors read as much about SJS research as we do?????
Someone mentioned that the 23rd is National Sjogrens Awareness Day. Maybe we should start working more on advocacy. I, for one, am sick and tired of being sick and tired.
I understand that mast cell stuff is generally better accepted in the UK and Canada. My American doctors don't pay it too much attention and kind of raise their eyebrows. I wish they would take it more serious as those with sensitive immune systems are easily confused and cause the self attacking. I am going to read the article entirely later today - thanks.