The prevalence of autoimmune disease in men is 3% versus 7.1% in women and both are rising; in the case of women, the disease often starts in ages between 15 and 44. About 24 million people in the US are affected by an autoimmune disease. However, a recent study (June 2020) indicates that the prevalence of a key autoimmunity biomarker is rising rapidly estimating that about 41 million individuals were already affected in 2012.

 

In rheumatoid arthritis (RA) the immune system attacks the joints; unlike osteoarthritis, which commonly affects older people, RA starts at 30 years of age or sooner. RA affected about 24.5 million people worldwide as of 2015; it is a chronic systemic disorder with lung fibrosis as a recognized complication. According to the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2017 study, almost 20 million people suffered of RA, while the US had the largest incidence increase (20.7%).

 

Psoriasis is a chronic autoimmune disease characterized by keratinocyte hyperproliferation; the excess cells build up and usually form red patches with silver-white scales of plaque on the skin. About 30% of psoriatic patients also develop swelling, stiffness, and pain in their joints: this form of the disease is called psoriatic arthritis; the inflammatory mediators (cytokines) found in the psoriatic joints of psoriatic arthritis patients are similar to those of psoriatic skin lesions, suggesting a common inflammatory mechanism. 

 

In the US, psoriasis prevalence is reported as 0.5% to 3.2%, affecting about 7.4 million people; globally 125 million are affected by the condition. Psoriasis affects about 3% of the Western world population; it is about five times more common in people of European descent than in people of Asian descent. It affects about 6.7 million persons in the US.

 

There is no cure for psoriasis; however, topical and/or systemic treatments help control the symptoms. Nearly a half of psoriatic individuals over 65 years old have at least three comorbidities (concurrent conditions), and two thirds have at least two comorbidities.

 

The annual cost for treating psoriasis in the US is estimated to be 32.5 billion USD, including $12.2 billion in direct costs. These costs increase significantly when comorbidities such as cardiovascular disease, diabetes or lung disease are involved: expenses linked to comorbidities are estimated at an additional $23,000 per person per year.

 

Importantly, preliminary research has suggested that antioxidants such as polyphenols may have beneficial effects on the inflammatory features of psoriasis (Dobois-Declercq S. and Pouliot R. 2013) and this effect is consistent with the effectiveness of dimethyl fumarate in treating moderate to severe psoriasis (Mrowietz 2017), since fumaric acid esters are able to elicit powerful antioxidant actions mediated by nuclear translocation of transcription factor Nrf2. In fact, oxidative damage mediated by free radicals is a hallmark of all autoimmune pathologies (Smallwood 2018).

 

Multiple sclerosis (MS) is an autoimmune disease associated with T-cell attack on the myelin sheath of brain and spinal cord neurons. MS is the most common immune-mediated inflammatory disorder affecting the central nervous system. In 2015, about 2.3 million persons were affected globally; that same year, about 18,900 people died from MS, up from 12,000 in 1990

 

There is no known cure for MS; life expectancy is on average 5 to 10 years lower than that of the general population. While there are medications to treat MS, these are only somewhat effective, can have serious side effects and be poorly tolerated.

 

Importantly, orally-administered dimethyl fumarate is one of the drugs being used to treat MS, as mentioned in connection with its use to treat psoriasis (see above), which strongly suggests that antioxidants are useful to counteract oxidative stress and inflammation in MS.

 

Overwhelming evidence supports the potential of H2S-based treatments in inflammatory/autoimmune diseases. Thus:

•  In type 1 diabetes, H2S protects the kidney from injury in mice (Papu-John 2019);

•  Psoriasis is associated with abnormally low blood levels of H2S (Alshorafa 2012) and responds favorably to exogenous H2S-based treatment (Rodrigues 2015, Schmidt 2015); 

•  Serum H2S levels of psoriatic patients are negatively correlated with clinical disease severity (Alshorafa 2012):

•  Psoriatic patients have significantly higher blood homocysteine (Hcy) levels compared to healthy controls. This is relevant because: This is relevant because:

1. Hyperhomocysteinemia is related to the occurrence and development of numerous diseases, such as atherosclerosis, neurodegenerative diseases, stroke, venous thrombosis, peripheral arterial disease and systemic sclerosis (Kim 2019, Lin 2019, Kumar 2018, Abdulle 2018);

2. Hyperhomocysteinemia causes behavioral and neurochemical alterations through decreased H2S production (Kumar 2017);

3. Hcy is a potential therapeutic target for psoriasis treatment (Lin 2019) since some psoriasis cases improve by lowering Hcy (Aronson 2017).

•  H2S inhibits he abnormal activation of lymphocytes in systemic lupus erythematosus (SLE) patients (Han 2013);

•  H2S delivers protective effects in systemic sclerosis (Wang 2016);

•  In vitro multiple sclerosis (MS) experimental results indicate MS be treated using H2S-releasing molecules (Talaei 2015);

•  Experimental autoimmune encephalomyelitis (EAE) is an animal model of brain inflammation; it is an inflammatory demyelinating disease that is widely studied as a model of human demyelinating diseases — including MS. The results of numerous studies of EAE in different animals (mice, rats, rabbits, guinea pigs, primates) have shown that EAE is intimately linked to dysregulation of immune cell function, oxidative damage to tissue, and upregulation of proinflammatory factors such as NF-kappa-beta, TNF-alpha and IL-6: importantly, H2S is known to effectively counteract oxidative stress and regulate immune function (Gojón 2020).