I think there is a connection between high iron levels and MS symptoms. I'm living proof of it. I have the C282Y gene, so does my sister with MS.
We both have highish iron levels. I developed my lesion when my transferrin saturation was at it's highest levels (note not "serum iron"), Serum Iron was never above high/normal levels. Transferrin saturation is not normally tested for (it was, once upon a time).
One good phlebotomy put me right back on my feet. It lasted six weeks, I'm going downhill again now. What happened to me, wonderful that it is, may be unique to me as I have high T-Lymphoctes because I am asplenic, much higher than most people I would guess. So the process was amplified in me, and the cure was also amplified.
The connections lies here, but please put me right Cheer if you will
Hypothetical molecular mechanisms by which local
iron overload facilitates the development of
venous leg ulcers and multiple sclerosis lesions
M. Simka a,*, Z. Rybak b
a Department of Angiology, Wodzislawska 78, 43-200 Pszczyna, Poland
b Department of Vascular, General and Transplantation Surgery, Medical University, Wroclaw, Poland
Received 4 December 2007; accepted 23 February 2008
Summary This paper presents a hypothetical model of role for iron in the development of venous leg ulcers and
multiple sclerosis. Elevated concentrations of iron were found in the skin affected by venous hypertension and also in
the areas of brain with multiple sclerosis lesions. Individuals with hemochromatosis gene (HFE) mutations: C282Y and
H63D, which result in a less efficient transport of iron by macrophages, are characterized by an increased risk for
venous leg ulcer and multiple sclerosis. Multiple sclerosis is a T cell-mediated disease, and T cells probably participate
in the development of venous ulcers. This deleterious role of ferric ions could be related to the regulation of T cell
proliferation and apoptosis. Under normal conditions excessive accumulation of T cells cannot take place, because
nitric oxide and interferon-gamma drive these cells toward apoptosis. However, in tissues with a high concentration of
iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INFcR2
chain of the interferon-gamma receptor, the downregulation of inducible nitric oxide synthase expression in
macrophages and the inactivation of the active site of caspases. Yet, it should be emphasized that this hypothesis does
not claim for the increased concentration of iron as a direct causal factor for the development of venous ulcerations or
multiple sclerosis, but rather, iron is a factor that modulates and exaggerates the autoimmune process. Iron chelators,
administered systemically or locally, should potentially exhibit therapeutic and prophylactic activity against venous leg
ulcers and multiple sclerosis.
and added to this:
J Vasc Surg. 2005 Aug;42(2):309-14.
Hemochromatosis C282Y gene mutation increases the risk of venous leg ulceration.
Zamboni P, Tognazzo S, Izzo M, Pancaldi F, Scapoli GL, Liboni A, Gemmati D.
Inter-Departmental Vascular Disease Center, University of Ferrara, Italy. email@example.com
OBJECTIVE: Chronic venous disease (CVD) is the most common vascular disorder, progressing in approximately 10% of cases toward chronic venous leg ulceration, whereas the hemochromatosis gene (HFE) C282Y mutation is the most common recognized genetic defect in iron metabolism. Because CVD leads to local iron overload in the affected legs, we investigated whether two common HFE mutations could increase the risk of chronic venous leg ulceration. METHODS: This was a case-control study at the Vascular Diseases Center, University of Ferrara, Italy. From a cohort of 980 consecutive patients affected by severe CVD (CEAP clinical classes C4 to C6) we selected 238 cases with the exclusion of any other comorbidity factor potentially involved in wound etiology (group A). They were subdivided into group B, including 137 patients with ulcer (classes C5 and C6: 98 primary and 39 postthrombotic cases), and group C, including 101 cases with no skin lesions (class C4). They were completely matched for sex, age, and geographic origin with 280 healthy controls (group D). A total of 518 subjects were polymerase chain reaction genotyped for HFE mutations (C282Y and H63D). We assessed the risk of ulceration by comparing the prevalence of ulcer in homogenous cases with and without the HFE variants. Other main outcome measures were the sensitivity, specificity, and predictive values of the genetic test in CVD cases. RESULTS: C282Y mutation significantly increases the risk of ulcer in primary CVD by almost seven times (odds ratio, 6.69; 95% confidence interval, 1.45-30.8; P = .01). Application of the HFE test in primary CVD demonstrated increased specificity and positive predictive values (98% and 86%, respectively), with negligible sensitivity and negative predictive values. CONCLUSIONS: The overlap of primary CVD and the C282Y mutation consistently increases the risk of developing venous leg ulceration. These data, which have been confirmed in other clinical settings, suggest new strategies for preventing and treating primary CVD. CLINICAL RELEVANCE: The number of patients affected by primary CVD is so great that the vast majority of ulcers are also related to this common problem. On the other hand, there is not a reliable way for identifying in advance, from the broad base of primary CVD patients (20-40% of the general population), the high risk minority (10% of primary CVD cases) who will develop a venous ulcer. In such cases, a simple C282Y blood genetic test demonstrated an elevated specificity in predicting ulcer development (98%, CI 95%, 92.8-99.7). The genetic test could be applied starting from the C2 class, varicose veins, the most common situation observed in clinical practice. In perspective, the presence of the C282Y mutation would strengthen the indications and priorities for surgical correction of superficial venous insufficiency.
PMID: 16102632 [PubMed - indexed for MEDLINE]
Publication Types, MeSH Terms
Surely there must be a tie in somewhere.