Acute Phase Phospholipids Related to the Cardiolipin of Mitochondria in the Sera of Patients With CFS, ciguatera, GWI, 2008. Hokama et al

[Sly Saint]

Acute Phase Phospholipids Related to the Cardiolipin of Mitochondria in the Sera of Patients With Chronic Fatigue Syndrome (CFS), Chronic Ciguatera Fish Poisoning (CCFP), and Other Diseases Attributed to Chemicals, Gulf War, and Marine Toxins

Yoshitsugi Hokama 1 , Cara Empey-Campora, Cynthia Hara, Nicole Higa, Nathaniel Siu, Rachael Lau, Tina Kuribayashi, Kenichi Yabusaki

Abstract
This study examined 328 CFS sera in a study with 17 CCFP, 8 Gulf War Veterans (GWV), 24 Prostate Cancer (PC), and 52 normal sera in the modified Membrane Immunobead Assay (MIA) procedure for CTX. Three hundred and twenty-eight CFS patients' sera were examined by the modified MIA with purified MAb-CTX and 91.2% gave a titre > or =1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV sera samples also had a titre > or =1:40. 92.3% of 52 normal sera showed titres of 1:20 or less, while 4 gave titres of > or =1:40. In addition, 41 sera were examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8% demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies.

These results showed mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum samples were examined for aCL, with 37 showing positive for aCL, representing 90.2% positive for the three disease categories examined: CFS, CCFP and GWV. Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients (CFS (18), CCFP (5), and GWV (5)) was negative for aM-M2. Inhibition analysis with antigens, CTX, CFS "Acute Phase Lipids", commercial Cardiolipin (CL) and 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL from patients' serum show that the phospholipids in CL and CTX are antigenically indistinguishable with antibodies MAb-CTX and CFS-aCL.

Preliminary chemical analyses have shown the lipids to be phospholipids associated with CL of the mitochondria. We designate this "Acute Phase Lipid" comparable to "Acute Phase Proteins" (C-reactive protein (CRP) and Serum Amyloid A (SAA)) in inflammatory conditions.

https://pubmed.ncbi.nlm.nih.gov/18348309/

 

[mariovitali]

The PDF version with the full paper can be found here :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649096/pdf/JCLA-22-99.pdf


From the paper :

We wish to designate these lipids as ‘‘acute phase lipids,’’ comparable to C-reactive protein (CRP) (18,19) and serum amyloid A (SAA) (20) symbolized in diseases triggered by cytokines in the inflammatory processes of these diseases in the liver

and

It is suggested that the increase in phospholipids associated with CL and all may be associated with defective mitochondrial metabolism and thus apoptosis in regulation of program cell death, especially involved in the immune system, hence immune dysfunction status in CFS disease

and

We have found that the ‘‘acute phase lipid’’ in the CFS lipid fraction appears to be associated with phospholipids (1,3-bis(sn-30 -phosphatidyl)-sn-glycerol) of mitochondria found in many serum samples of diseases including viral infections (Epstein-Barr, hepatitis viruses, and human immunodeficiency virus [HIV]), parasitic diseases, marine toxins (CTX, okadaic acid, palytoxin, polyether lipids), and other microbial infectious diseases

Here is where the Liver comes into play :

(CFIDS) Foundation press release that CFS/ myalgic encephalomyelitis (ME), multiple sclerosis (MS), and idiopathic epilepsy, and CFS were caused by a Cryptovirus (Zoonotic virus), similar to the parainfluenza virus-5, originally found in swine (17). These disease processes, particularly CTX, most likely affect the major organ, the liver. Since phospholipid release is suspected, it is the mitochondria of these cells in the liver that is thought to be affected during the detoxification or destruction of the toxic entity. We hypothesize that damage or stimulation of the mitochondria results in the release of phospholipids, which in turn induce production of an autoimmune antibody (antiphospholipids). Many of the disease states listed above have been found to involve antiphospholipids, including autoantibodies to cardiolipin (CL) of the immunoglobulin G (IgG), IgM, and IgA isotypes.

So Liver, cardiolipin antibodies, antiphospholipids. They mention that the toxin CTX (ciguatoxin) is most likely affecting the Liver but they also suggest that Liver involvement may hold for other cases as well :


Next let's look at Anti-phospholipids :


from : https://www.york-me-community.org/s...d-fibromyalgia-the-dysautonomia-conference-4/

As if we needed another syndrome. Chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), fibromyalgia (syndrome), irritable bowel syndrome (IBS) are old-timers in the ME/CFS/FM world. In the last couple of years, mast cell activation syndrome (MCAS) and Ehlers Danlos Syndrome (EDS) joined the party. Sjogren’s Syndrome (SS), which was all over the Dysautonomia International conference, may be a late entry, and now it seems we can add antiphospholipid antibody syndrome (APS) – which is apparently very common in POTS – to the list of syndromes...

Cardiolipin antibodies in ME/CFS, same authors .Has this been replicated? :

Anticardiolipin Antibodies in the Sera of Patients With Diagnosed Chronic Fatigue Syndrome
Yoshitsugi Hokama 1, Cara Empey Campora, Cynthia Hara, Tina Kuribayashi, Diana Le Huynh, Kenichi Yabusaki
Affiliations

• PMID: 19623655
  
• PMCID: PMC6649060
  
• DOI: 10.1002/jcla.20325

Free PMC article
Abstract

Examination of anticardiolipin antibodies (ACAs) in the sera of patients clinically diagnosed with chronic fatigue syndrome (CFS) using an enzyme-linked immunoassay procedure demonstrated the presence of immunoglobulin M isotypes in 95% of CFS serum samples tested. The presence of immunoglobulin G and immunoglobulin A isotypes were also detected in a subset of the samples. Future studies will focus on elucidating whether alterations to mitochondrial inner membranes and/or metabolic functions play a possible role in the expression of ACAs.

https://pubmed.ncbi.nlm.nih.gov/19623655/



FWIW, using some new techniques that attempt to find the cause (highly experimental) suggest -as a hypothesis as always- that the most likely causative problem is in the Mitochondria-associated Membranes (MAMs).

 

[wigglethemouse]

For those in the US that are interested here are a couple of antiphospholipid Syndrome diagnostic tests from Quest that include testing for anti-Cardiolipin (aCL) antibodies.

Antiphospholipid Syndrome Diagnostic Panel
https://testdirectory.questdiagnost...spholipid-syndrome-diagnostic-panel?cc=MASTER

Antiphospholipid Antibody Panel
https://testdirectory.questdiagnostics.com/test/test-detail/14890/?cc=WDL

Dr Jill Schofield has talked about this disease in her presentations on complex chronic disease patients she sees. Here is an excerpt from her website. In simple terms "sticky blood".
https://www.centerformultisystemdisease.com/services/antiphospholipid-syndrome

Antiphospholipid syndrome (APS) is an autoimmune blood clotting disorder that may cause recurrent miscarriage or stillbirth as well as other serious problems like strokes, heart attacks and blood clots in the lungs (pulmonary embolus) and/or legs (deep vein thrombosis). APS also causes a number of other problems, including neurological disorders such as severe migraines, memory loss, dysautonomia and seizures. APS presents most often in people under the age of 50 and it may also affect children.

I've heard of a few ME/CFS folks testing positive for these.

 

[Mithriel]

The research was done in Hawaii but I believe the main scientist retired or, possibly, died and the research joined all the rest of the promising ME work that just faded away.

I seem to remember reading that one of the problems was that the Hawaii work tended to talk about ciguatoxin but the work from the NIH spoke about anticardiolipin. Even though these were the same thing, it meant that the quantity of research seemed half of what it actually was.