Endothelial dysfunction and HSP60 antibodies – pieces to the ME/CFS puzzle?

Endothelial dysfunction – ME/CFS

Vascular endothelial dysfunction has been measured directly in ME/CFS patients. This information is from: International Journal of Cardiology, 2012 Feb 9; 154(3):335–6

ME Research UK has described the study here: Large and small artery endothelial dysfunction in chronic fatigue syndrome

This study is indeed interesting, because endothelial dysfunction in ME/CFS patients is also discussed in this presentation from the Research Council of Norway made by Øystein Fluge and Olav Mella from Haukeland University Hospital: B-lymfocytt deplesjon og sykdomsmekanismer ved kronisk utmattelsessyndrom/ myalgisk encephalopati (ME/CFS)

ME/CFS - HSP60

Hsp60 is of  interest in ME/CFS because of this recent study Epitopes of Microbial and Human Heat Shock Protein 60 and Their Recognition in Myalgic Encephalomyelitis:

"When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity."

ME Research UK has described the study here: Immune responses to HSP60

HSP60 - endothelial cells – autoimmunity - inflammation seem to be connected

Modulation of endothelial cell damages by anti-Hsp60 autoantibodies in systemic autoimmune diseases

and

Chlamydia heat shock protein 60 decreases expression of endothelial nitric oxide synthase in human and porcine coronary artery endothelial cells

Endothelial dysfunction and HSP60 antibodies are found in Behçet's disease and Ankylosing spondylitis. Endothelial dysfunction may also be involved in the pathobiology of depression. So, endothelial dysfunction and HSP60 antibodies are not unique for ME/CFS, but perhaps it can help us to put the pieces together and understand the disease.

Let us look at my “pieces to the ME/CFS puzzle”:

ME/CFS - autoimmune thyroiditis – endothelial dysfunction - HSP60

From this German report "Characterization of phenotypic and functional Immune status of patients with Chronic Fatigue Syndrome": Charakterisierung des phänotypischen und funktionellen Immunstatus bei Patienten mit Chronischem Erschöpfungssyndrom, we can read that (my translation):

“Our analyzes have shown that an increased prevalence (approximately 11%) of autoimmune thyroiditis (Hashimoto's thyroiditis) is present in CFS patients. In contrast, the prevalence of autoimmune thyroiditis in the normal population is about 1.5 -2% . This finding suggests involvement of autoimmune processes in the pathogenesis of CFS. It is a primary thyroid hypothyroidism, which belongs to the most common consequences of an autoimmune disease.”

The endothelial dysfunction:

Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto'sthyroiditis

And there is a HSP60 connection:

Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis

ME/CFS – POTS – endothelial dysfunction(?) - HSP60

ME/CFS and Postural Orthostatic Tachycardia Syndrome (POTS) are two diseases which very often occur together. One study showed that 27% of ME/CFS patients had POTS. A second study showed that 64% of a group of POTS patients also met the criteria for ME/CFS. Orthostatic intolerance can be a part of an autonomic dysfunction (like POST) is in a study shown to occur in 95% of ME/CFS patients.

Like ME/CFS, POTS is suspected to be an autoimmune disease. In this article, Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome, we find (on page 6, table 3) HSPD1 60 kDa heat shock protein as a “suspect” for a possible autoimmune attack.

And links about ME/CFS/POTS, endothelial function and blood flow:

In ClinicalTrials.gov Identifier: NCT01308099 we find this project: Assessment of Vascular Endothelial Function in Postural Tachycardia Syndrome The hypothesis of the study is: Patients with POTS will have vascular endothelial dysfunction compared with control subjects.

Flow-mediated vasodilation and endothelium function in children with postural orthostatic tachycardia syndrome: In conclusion, augmented Flow Mediated Dilation and abnormal function of vascular endothelium may play an important role in POTS in children.

Decreased microvascular nitric oxide-dependent vasodilation in postural tachycardia syndrome: One variant of postural tachycardia syndrome (POTS), designated low-flow POTS, is associated with decreased peripheral blood flow related to impaired local vascular regulation. The data suggest that flow-dependent nitric oxide release is reduced in low-flow POTS. This may account for local flow regulation abnormalities.