The role of immunoglobulines E
In January 2020 we published together with 3 medical doctors from Africa: “Jérôme, Munyangi, Pascal Gisenya, Patrick Ogwang …Immunoglobulins in the skin lead to long-lasting prophylaxis. Pharm Pharmacol Int Journal, PPIJ, 2020, Issue1”, a paper which, if widely spread, could have had a dramatic impact on the way the present Covid-19 crisis is handled.
One of the key findings of their work is that immunoglobulins are higher in malaria endemic areas.
The total IgE level in a population is strongly related to the malaria endemicity in that area with concentrations over 500 ng/ml, with many values over 2000 ng/ml. In the European population its concentration is low at 10 to 300 ng/ml. For example, 10 ng/ml in Sweden, 647 in Thailand, 2134 in Liberia.
H Perlmann, H Helmby, IgE elevation and anti-malarial antibodies in Plasmodium falciparum malaria. Clin Exp Immunol. 1994 Aug; 97(2): 284–292
Perlmann P, ElGhazali G, Blomberg MT: IgE and tumor necrosis factor in malaria infection. Immunol Lett. 1999, 65: 29-33. 10.1016/S0165-2478(98)00120-5.
This higher IgE level in endemic areas protects against Plasmodium infections. It is likely that it also protects against viral infections.
The production of IgE specific to different viruses strongly suggest an important role for these antibodies. 40 years ago, it was found that naturally occurring viral respiratory infections increased serum IgE levels in both nonatopic as well as atopic individuals. They decreased after the symptoms. But infected and/or vaccinated children and adults continue a long-term production of IgE anti-Influenza virus antibodies long term. The long -term production, up to two years, of IgE anti-Influenza virus antibodies may contribute to protective immunity against Influenza.
L Perelmutter, L Potvin, P Phipps. Immunoglobulin E Response During Viral Infections. J Allergy Clin Immunol. 1979 Aug;64(2):127-30.
Tamar A Smith-Norowitz , Darrin Wong, Martin H Bluth. Long Term Persistence of IgE Anti-Influenza Virus Antibodies in Pediatric and Adult Serum Post Vaccination with Influenza Virus Vaccine. Int J Med Sci. 2011 Mar 18;8(3):239-44. doi: 10.7150/ijms.8.239.
O L Frick. Effect of Respiratory and Other Virus Infections on IgE Immunoregulation. Review J Allergy Clin Immunol. 1986, 1013-8.
Artemisia and Covid: friend of foe?
If malaria protects against the corona virus this entails a crucial question: any reduction of malaria infections might lead to an increase in viral infections.
The conclusion we reached is that the Artemisia plants protect against both, malaria and virus, but artemisinin and derivatives only reduce malaria but may enhance viral infections. This hypothesis of course needs further research.
The prophylactic efficiency of Artemisia annua was first discovered and documented by Patrick Ogwang in several papers.
Ogwang Patrick Engeu: Evaluation of Artemisia annua L for Malaria prophylaxis. Doctoral Thesis. Makerere University. 2012. Reg. Number 2008/HD 17/4952U
In a Chinese trial a significant boosting of IgGs was noticed by the administration of the aqueous extract of Artemisia rupestris.
Zhang A, Wang D, Li J, Gao F, Fan X, the effect of aqueous extract of Artemisia rupestris L. (an influenza virus vaccine adjuvant) on enhancing immune responses and reducing antigen dose required for immunity. PLoS ONE 2017, 12(8): e0183720
IgE elevations are the expression of CD4+ cells and we have been able to demonstrate that these are increased by the administration of Artemisia annua and Artemisia afra. CD4+ cells are already induced in the pre-erythrocytic stages of malaria. This leads to a wide range of antibodies including some specific immunoglobulines.
Constant Kansango Tchandema, Pierre Lutgen. In vivo trials on the therapeutic effects of encapsulated Artemisia annua and Artemisia afra. Global Journal for Research analysis 2016, 6, 228-234
D Perez-Mazliah, J Langhorne. CD4 T-cell subsets in malaria revisited: Frontiers in Immunology, 2015,5, article 671
This is in line with information received from Patrick Ogwang, Mbarara University: Artemisia annua drinking raises immunoglobulines.
However, monotherapy with artemisinin may have the opposite effect. In a study in China artesunate suppressed the humoral immune responses.
P Y Lin, Z M Feng, J Q Pan, D Zhang, L Y Xiao. Effects of Artesunate on Immune Function in Mice. Zhongguo Yao Li Xue Bao. 1995 Sep;16(5):441-4.
Even worse, several papers report haemolytic anemia after treatment with artemisinin derivatives and particularly with IV artesunate
K Rehman, F Lorsch, P Kresmner. Hemolysis associated with the treatment of malaria with artemisinin derivatives: a systematic review of current evidence. Int J Infect Dis, 2014, vol 29 268-273
Serious side effects were also reported in France after IV artesunate treatment. Artesunate decreases hemoglobulin, platelets, erythrocytes and immunoglobulins
Martin Danis, Marc Thellier, Le paludisme grave à P. falciparum en France, 2000-2011 : évolution épidémiologique et nécessité d’une nouvelle prise en charge thérapeutique. Bull Acad Nat Méd 3, 699-716, 2013
How do IgE protect against viral invasion?
The main entry port for viruses are mucosal tissues and skin.
The skin of most animals is an effective barrier against viral infections. However, viruses can pass through cuts or abrasions. Antibodies migrate and bind to wounded tissues. Antibodies could block invasion in several ways.
A recent paper highlights an important finding. After plasma infusion, IgE in the vascular circulation and serum had a half-life of 2 days but positive skin tests results were still demonstrated after 50 days. This long-life of the IgE in the skin may play an important role in prophylaxis.
MG Lawrence, JA Woodfolk, Half-life of IgE in serum and skin. J Allergy Clin Immunology, 2017, 139, 422-428.
IgE also accumulate in keratotinocytes and epithelial cells and contribute to the barrier properties. Some people apply wormwood directly to the skin for alleviating insect bites.
O Kortekangas-Savolainen, S Peltonen, K Pummi, IgE-binding Components of Cultured Human Keratinocytes in Atopic Eczema/Dermatitis. Allergy. 2004 Feb;59(2):168-173
Sabine Altrichter, Ernst Kriehuber, Serum IgE Autoantibodies Target Keratinocytes in Patients with Atopic Dermatitis Journal of Investigative Dermatology (2008) 128, 2232–2239
Immunoglobulin E can be highly elevated in the airway mucosa and in saliva independently of IgE serum levels. IgE that is locally produced in the target organ could have diagnostic and therapeutic importance. These antibodies could block infections in several ways.
E A Grönblad. Concentration of Immunoglobulins in Human Whole Saliva: Effect of Physiological Stimulation. Acta Odontol Scand1982;40(2):87-95
A few decades ago, the almost complete absence of infectious HIV in saliva was noticed. Inhibition of HIV may be partly due to several inhibitors of viruses that are present in the saliva. Incubation of HIV-1 with human saliva followed by addition of the mixture to susceptible cells leads to partial or complete suppression of viral replication in vitro.
Malamud D, Abrams WR, Barber CA. Antiviral Activities in Human Saliva. Adv Dent Res. 2011 Apr; 23(1): 34–37.
Fultz PN Components of saliva inactivate human immunodeficiency virus. Lancet. 1986; 2:1215
It was found that age differences were much greater in salivary antibodies than in serum; older adults had reduced salivary secretion rates of IgA and IgE. This decline in local immunity may contribute to increased infection risk in the elderly, as it was seen in the Covid-19 pandemics.
Abdollah JafarzadehI; Mostafa SadeghiII. Salivary IgA and IgE levels in healthy subjects: relation to age and gender. Braz. oral res. 2010, vol.24 no.1