Nov
21
2020

Antibody Treatment for Rheumatoid Arthritis Was Superior

Researchers found that antibody treatment for rheumatoid arthritis was superior to conventional therapy. In particular, rheumatoid arthritis is an autoimmune disease where autoantibodies attack the synovial lining of joints. In this case, subsequently macrophages are activated, which attack joint surfaces. As an illustration, this process leads to crippling joint deformities.

The original study was published in June, 2019, but this is difficult to understand. The magazine Sciworthy published a review article on August 24, 2020 with more understandable language.

To emphasize, in mouse experiments the researchers found that only a small subfraction of activated macrophages caused symptoms of rheumatoid arthritis. They were folate receptor beta (FR-β) positive macrophages. It is important to realize that the researchers found them both in mice with rheumatoid arthritis and in man. The evidence in humans were the same findings in human tissue samples of people with autoimmune diseases.

Details of mouse experiments

Folate receptor beta (FR-β) positive macrophages are key in mouse model of RA

Explicitly, the researchers started experiments with a mouse model of rheumatoid arthritis, because it is easier to do than human research. They found that the key to developing rheumatoid arthritis was the presence of folate receptor beta (FR-β) positive macrophages. Chiefly, macrophages remove cell debris, bacteria or viruses from the blood. However, once they are activated and they carry FR-β receptors on their surface, they destroy joints. Certainly, in the mouse model monoclonal F3 antibodies were developed that kill activated macrophages. On the contrary, the human equivalent for the F3 antibodies is monoclonal antibodies with the name m909. They are directed at the FR-β receptors on the surface of activated macrophages. But first to the mouse experiments.

Inflammation from intraperitoneal injection of thioglycollate

In the first place, the researchers created an inflammatory condition by injecting thioglycollate into their peritoneal cavity. They could demonstrate that inflammation did occur. With this in mind they found macrophages in the peritoneal fluid. There were a lot of activated macrophages in it. Histological slides were analyzed with the help of F3 antibodies. In this case they visualized the activated macrophages. Subsequently the researchers treated mice with varying concentrations of monoclonal F3 antibodies. They found that the higher concentrations cured intraabdominal inflammation of the mice.

Researchers used monoclonal F3 antibodies to treat mouse model of RA

The researchers treated collagen-induced arthritis next in a number of experiments. Several concentrations of monoclonal F3 antibodies were given to these mice. Other experiments showed that monoclonal F3 antibodies specifically attacked only the activated macrophages and killed them. The killing of the activated macrophages in the mouse model of rheumatoid arthritis cured the arthritis. Fig. 5 shows this.

Mice treated with maximum concentrations of monoclonal F3 antibodies showed decrease in bone density

Next the researchers treated rheumatoid arthritis mice with maximum concentrations of monoclonal F3 antibodies to treat the arthritis. The swelling of their paws went down completely. CT scans of the bone in the paws showed decrease in bone density, while untreated controls showed significant loss of bone density. Monoclonal F3 antibodies were indeed a cure for RA in mice (Fig. 6).

Human experiments

Researchers confined human experiments to tissue samples from patients with various autoimmune diseases. Skin biopsies from patients with psoriasis, scleroderma, and sarcoidosis showed the distribution of FR-β-positive macrophages by special staining. This staining technique used human monoclonal antibodies (m909) against human FR-β receptors on activated macrophages. The publication depicts images that show abundant activity in all three autoimmune diseases (Fig. 1).

Researchers examined tissue samples from other autoimmune diseases with monoclonal antibodies (m909) against human FR-β receptors. The activated macrophages including rheumatoid arthritis, Crohn’s disease, ulcerative colitis and idiopathic pulmonary fibrosis lit up on fluorescence microscopy. In addition, nonspecific interstitial pneumonia, chronic obstructive pulmonary disease, systemic lupus erythematosus, psoriasis, and scleroderma tested positive as well.

Future therapy possibilities of rheumatoid arthritis with monoclonal antibodies

A series of experiments showed that two mechanisms can eliminate FR-β-positive macrophages: complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity. It means that there is a strong possibility that autoimmune diseases may be treatable with monoclonal antibodies. Fig. 2 summarizes these experiments.

Conventional therapy for rheumatoid arthritis

To explain, the conventional treatment approach of rheumatoid arthritis is to induce a disease remission with drugs. To this effect doctors use anti-inflammatory drugs like ANSAIDs, disease modifying anti-rheumatic drugs (DMARDs). For example, drugs like methotrexate and sulfasalazine belong into this category. Unfortunately, the conventional drugs have many serious side effects that often make the rheumatoid arthritis patient’s condition worse.

In contrast, the integrative medicine approach to rheumatoid arthritis is to use dietary measures to reduce the inflammation. The fasting mimicking diet is able to reduce the severity of the inflammation in RA patients.

Other authors described the use of the Mediterranean diet to reduce inflammation. In addition, there are a number of regenerative methods that help improve the condition of RA patients. Research described here proved that antibody treatment for rheumatoid arthritis was superior to conventional therapy in a mouse model.

Discussion

Monoclonal antibodies (m909) against human FR-β receptors targeting activated macrophages opened up a new therapy method against rheumatoid arthritis. The equivalent F3 antibodies in mice were a useful tool to expedite research in this field. The publication that I reviewed here was able to combine mouse experiments and work on human tissue samples essentially showing the same results . Monoclonal antibodies (m909) against human FR-β receptors work potentially like a broad-spectrum anti-inflammatory drug. The monoclonal antibodies reduce the accumulation of inflammatory immune cells, which treats the cause of rheumatoid arthritis. This will likely be the future cure of rheumatoid arthritis and other autoimmune diseases. We urgently need clinical trials to prove in humans that the findings from a mouse model and human tissue samples are correct.

Antibody Treatment for Rheumatoid Arthritis Was Superior

Antibody Treatment for Rheumatoid Arthritis Was Superior

Conclusion

Researchers recently showed in a mouse model that a small portion of activated macrophages cause rheumatoid arthritis (RA). But they also examined many biopsies from patients with autoimmune diseases. The findings in human tissue samples were identical to the findings in a mouse model. Activated macrophages are sensitised to attack the linings of joints as is the case with rheumatoid arthritis. These macrophages develop special receptors, called folate receptor beta (FR-β), and the macrophages release cytokinins. The cytokinins (TNFα, IL-1, IL-6, IL-12 and others) cause inflammation and make the RA worse. They also recruit more neutral macrophages and convert them into activated macrophages. The research group found that monoclonal antibodies against human or mouse FR-β receptors killed the activated macrophages. This alleviated the arthritic symptoms and after enough antibody treatments cured the RA. There were no negative effects on the rest of the immune system.

Physicians will cure human autoimmune diseases with monoclonal antibodies in the future

Researchers demonstrated this mostly in a mouse model. But the authors have manufactured human monoclonal antibodies against the FR-β receptors of activated macrophages. This has set the stage for curing human autoimmune diseases with monoclonal antibodies as well. At this point there is a need for clinical trials with various autoimmune diseases including rheumatoid arthritis with monoclonal antibodies against activated macrophages.

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May
07
2016

Sun Exposure Helps Many Symptoms

For the past few years it has become evident that sun exposure helps many symptoms. Patients with psoriasis have skin plaques on their skin. With sun exposure some of them disappear and the skin appearance improves. Patients with seasonal affective disorder have worsening of their depression over winter. Depression lifts with more sun exposure in the spring. Even a complicated disease like MS, which is more common in the northern latitudes, improves with sun exposure or a move to the southern states.

Osteoporosis: sun exposure has a positive effect

Osteoporosis was the subject of an April 2016 study from Argentina.

The researchers counted the amount of actinic keratosis lesions on the skin of subjects. This correlated well with lifetime sun exposure. Next they measured the  occurrence of hip fractures from osteoporosis. There was a correlation of the two. This case control study had 51 patients with hip fractures. Controls were 59 patients from the same hospital without hip fractures. The mean age was 80 years of age. 23.5% of patients with a history of hip fractures were observed to have actinic keratoses. In contrast 40.7 % of actinic keratoses were found in controls.

Sun exposure prevents hip fractures

The authors conclude that higher sun exposure is protective of hip fractures, but led to more actinic keratoses. They also stated that higher actinic keratoses rates, which are precancerous skin lesions are a risk for developing skin cancer. It is important to balance risk of osteoporosis from a lack of sun exposure with the risk of skin cancer from overexposure to the sun.

We know that higher doses of vitamin D3 in combination with vitamin K2 and calcium supplementation prevent osteoporosis. Reasonable daily doses are 5,000 to 10,000 IU of vitamin D3 per day, 200 micrograms of vitamin K2 per day and 500mg of calcium daily.

Psoriasis: sun exposure helps many symptoms

Psoriasis is an inflammatory condition of the skin with plaques and a characteristic skin rash. This February 2016 study from Turkey showed significant differences between women with psoriasis versus controls. Bone density studies showed lower levels in psoriatic females than in female controls. Female psoriasis patients had lower vitamin D levels than female controls. Male psoriatic patients showed no difference from controls. Low levels of vitamin D3 may be triggers for osteoporosis to develop in female psoriasis patients. Inflammation may also be a contributory factor. There was an elevation of the C-reactive protein (CRP) in female psoriasis patients.

Clinical observations have shown for years that the rash of psoriasis patients tends to improve during the summer.

Seasonal affective disorder: sun exposure lifts the mood

Seasonal affective disorder (SAD) has been known to respond to light therapy. Typically it peaks in the winter months and presents in mostly females who live far away from the equator. They improve when they travel to a sunny spot such as the subtropics or the southern states of North America during the winter months. But light therapy, vitamin D3, antidepressant therapy and counseling the mood swings of seasonal affective disorder will lessen.

In this 2014 study it was shown that depression in older people was not related to the darker months (between October and March). The summer depression rates in older people were identical to the winter depression rates.

Clinical trials with seasonal affective disorder (SAD) patients

In a group of 38 patients with SAD 14 patients were treated with white light visors, 15 with infrared visors and 9 served as a control (visors, no light). Both white light and infrared treated groups showed prevention of SAD while the control group developed SAD.

A 6-week trial was published March 2015. It involved 78 patients (51 Afro-Americans and 27 Caucasians). They all had SAD and received a treatment with 10,000-lux bright light for 60 min daily in the morning. Caucasians had a response rate of 75%. African-Americans had a response rate of only 46.3%. The investigators found that the symptomatic improvement and the rate of treatment response were the same in both groups. The researchers found that the Afro-American subgroup of patients required more education resources. This can overcome the inconsistent application with the bright light.

Vitamin D trials regarding SAD patients

In a study involving 185 female undergraduates of the Pacific Northwest, vitamin D blood levels were measured and a correlation of low vitamin D with depressive symptoms was found in SAD patients.

In a small study the hypothesis was tested that vitamin D3 in higher doses would be beneficial for SAD patients. Eight subjects received a treatment with 100,000 I.U. of vitamin D3, while seven subjects received phototherapy. All subjects had their vitamin D blood levels checked. Interestingly the vitamin D3 group improved on all depression scales. The phototherapy did not show improvement on the depression scale. The vitamin D level increased 74% in the vitamin D3 group and 36% in the phototherapy group.

Light exposure and vitamin D supplementation for SAD

All of these studies seem to indicate that SAD is more common in a younger population while in older people depression seems to be year-round. SAD does respond very well to 1-hour exposure of 10,000 lux of light in the morning. On a sunny day a walk in the sun for 1 hour is equivalent to an exposure at home with a SAD light. High dose vitamin D3 supplementation makes sense as low vitamin D levels were a persistent finding among SAD depression patients.

Multiple sclerosis: sun exposure makes a difference

Multiple sclerosis (MS) is more common in northern latitudes of the northern hemisphere. It is thought that sun exposure leads to higher vitamin D3 production in the skin, which prevents MS. On the other hand, once the diagnosis of MS is certain sun exposure or high doses of vitamin D3 can make it better.

This 2015 Australian study showed the same findings with a large group of MS patients.

This 2015 study from Sweden indicates that there is a compelling connection of prevention of MS through sun exposure or the taking of supplements of vitamin D3. In view of this evidence the authors suggest that you should take vitamin D3 supplements for prevention of MS before trials confirm this further.

Sun protection needed to prevent skin cancer

We have been hearing the slogan “slip, slop and slap” for skin cancer prevention. Slip, slop and slap stands for: slip on a shirt; slop on the sunscreen and slap on a hat. This publication dated March 2016 questions whether the precautions have been too zealous.

On the other hand the statistics regarding higher precancerous actinic keratoses in patients without osteoporosis are alarming too. It seems better to use high doses of vitamin D3, which will prevent osteoporosis, depression (SAD), MS and also improve psoriasis. Sun protection has decreased skin cancer, but did not curtail melanoma rates because sunscreen lotion can be penetrated by infrared radiation.

Use common sense for skin cancer prevention

This means that you should listen to the advice to stay out of the intense sun between 11AM and 3PM. Use vitamin D3 supplements in higher doses as this protects your skin. Research from England indicates that melanoma patients are usually the ones that are susceptible to melanoma genetically. They also have low vitamin D levels in the blood to a certain degree from skin cancer formation. The researchers recommend strongly that those at risk for melanoma need to be on higher vitamin D3 supplementations. A patient with a diagnosis of melanoma should receive high doses of vitamin D3.

Sun Exposure Helps Many Symptoms

Sun Exposure Helps Many Symptoms

Conclusion

It is not a myth: sun exposure helps many symptoms as explained above. Diverse body systems like osteoporotic bones, psoriatic skin and seasonal affective disorder respond to sun exposure. Sun exposure also prevents MS, a degenerative central nervous system disorder. The effects of vitamin D3 can explain some of this effect. It likely stems from sun exposure to the skin. But sunlight has hormonal effects. This occurs through the optic pathways and connections to the hypothalamus. We know that the sun helps combat many symptoms, but more research will be necessary, till we know exactly how it works.