One Health International – epidermolysis bullosa

Biological products PC2. Part 3. Active immunity via passive immunity

Ionel Victor Pătraşcu1a,b, Constantin Chiurciua, Viorica Chirciua, Mariana Oporanua, Iuliana Mihaia, Lucica Simaa, Georgiana Radua, Georgiana Topilescua, Cristina Căşarua

  1. Romvac, Limited Company, Voluntari, Romania
  2. Imunomedica-P, Bucharest, Romania

Abstract

The mechanisms of action of immunologically active proteins (IAP) in the human body are presented as well as some results concerning the treatment of psoriasis and epidermolysis bullosa.

Key words: immunologically active proteins, psoriasis, epidermolysis bullosa

Romvac has been conducting human and veterinary medicine research and production activities for over 50 years. It all started from the need for human and veterinary vaccines prepared on specific pathogen free (SPF) poultry [1]. SPF poultry were used for the production of human and veterinary vaccines on embryonated eggs and on whole SPF embryo tissue cultures, for research and control of biological products. Genetic studies were carried out at the SPF farms of Romvac regarding the role of sensitive and resistant allele in oncogenic virus-susceptible and -resistant SPF chicken. On this occasion, studies at Cornell University, Ithaca, NY. USA and Romvac demonstrated that in any genetic cross-combination the progenies with minimum one sensitivity allele are susceptible to developing the malign lymphoma called Marek’s Disease. It was proven to this extent that the sensitivity allele is dominant in any type of combination passed on to the progenies [1,2,3].

These activities were carried out in collaboration with specialists from Houghton Poultry Research Station, England and from Cornell University, Ithaca NY, USA.

Studies on oncogenic viruses were conducted at the same time in humans and animals, in collaboration with famous Romanian and American professors having constant support from the WHO. The activity in this field enabled us to discover in 1989 the greatest AIDS outbreak in children throughout the world, which ended in 1989 due to the first AIDS prevention and control program in Romania that was implemented together with the WHO [4-9]. Human and animal pathology studies expanded to the matter of antibiotic resistance for which we organized a similar research program that was different from that of other research institutes in the world.

Such studies were based on the active immunity produced in the body of animals and humans by oral administration of IAP. The immunologically active proteins (IAP) cross the digestive mucosa and reach the protein molecules that carry the V-variable, including lymphocytes B and T which they are directly effective against by transfer of target antigenic epitopes information. This information is absorbed differently by lymphocyte B and lymphocyte T respectively, each of these cells having distinct reactions. In the bone marrow, IgY is effective on the initial embryonic structures of lymphocyte B and produces hyperactive lymphocytes B ten times more effective than the lymphocytes which have not reached IgY. The naïve lymphocyte T absorbs the negative information from the V-variable of IgY and transfers it to its own DNA which is to be cloned. This new mature lymphocyte reaches the hyperactive lymphocyte B where it transfers the negative information from the V-variable of IgY and stimulates idiotypic IgY-identical IgG production. The amount of antibodies produced in the animal organism corresponds to a vaccination with an attenuated live virus. This mechanism represents a part of the effects of immune modulators and immunologically active proteins in the human organism.

The preclinical and clinical studies conducted during 2012-2016 revealed that we possess a set of immunologically active proteins (IAP) obtained on chickens (Gallus domesticus).

These products that have been prepared for the first time in the world, are completely different from the biological products currently used for psoriasis treatment and for other immune disorders in humans as well.

The biological products prepared on mono-clonal antibodies or their protein structures are murine or human proteins considered as “non self” by the human organism, with adverse or idiotypic reactions against them. This group of products structured on mammalian molecules (mice, humans) is considered as “non self” in the human organism and induces multiple and violent adverse or idiotypic reactions that, within 10-14 days, reduce or even destroy these products in the human body. The parenteral administration of these products was shown to be inappropriate and harmful resulting in severe local and general reactions and even anaphylactic shock, which are life-threatening for people. Such products are to be replaced as soon as possible based on the recommendations from the European Food and

Drug Administration, CDC Atlanta, Ge., ECDC Europe and from the scientific observations of certain specialists from EU, Japan, USA, Canada [10-15].

IAP are products obtained from poultry, that are phylogenetically 350 million years away from humans, more immunologically active than IgG of mammals, which are 35 million years away from humans. Under these conditions, the chicken reacts distinctly from mammals, including humans. Compared to monoclonal antibodies, IAPs are able to identify a large number of epitopes on the structure of the antigen and have specific effect against bacteria, viruses, fungi, unicellular parasites and even round worms. IAPs are specific and neutralize toxins, including exotoxins A and B caused by Clostridium difficile

(Patrascu et al., unpublished data).

In the human body, IAPs are considered as “self” and induce no adverse or idiotypic reactions. Therefore, treatments have been carried out for 14 years on daily basis in humans, without adverse or idiotypic reactions throughout the treatment period.

Modern psoriasis treatment consists of biological drugs (-ximab, -xumab, -umab, -cept) with a few deficiencies like blocking of certain cell functions and annihilation of parenterally administered cytokines, threatening the patient’s health due to some severe adverse and idiotypic reactions.

The emergence of antidrug antibodies (ADAS) against biological products resulted in functional or structural damage of biological products within 14-20 days post administration. ADAS may restrict the use of biological products for treatment of psoriasis, rheumatism and other diseases.

IAPs have a number of benefits compared to biological products, such as: interaction of V-variables, mucosal absorption, immunologically active proteins, big phylogenetic distance from humans, no adverse or idiotypic reactions, possibility of long-term treatment.

Preclinical research activities at ROMVAC were carried out at the same time with studies on treatment of antibiotic-resistant germ infections in humans, obtaining very good results in the treatment of urinary infections, prevention and treatment of nosocomial infections and treatment of respiratory tract infections.

 

RESULTS AND DISCUSSIONS

Psoriasis vulgaris treatment

Within the last two years we have started a treatment program for skin infections, on which occasion we found out that we could treat

ONE HEALTH INTERNATIONAL JOURNAL, 3(2),2017

psoriasis vulgaris using IAPs (more than 300 patients). Considering the properties of these proteins and the fact that for 14 years of study they have been accepted as “self” by the human body without inducing any adverse or idiotypic reactions, IAPs represent a scientific issue of particular importance. IAPs were used in children, resulting in healing of five of the 20 psoriasis children. The other children are still under treatment and their condition has improved. Another interesting fact of psoriasis children treatment is the wellbeing state that occurs in children and their parents as well. Preventive treatment is still administered in the cured children.

It has been for the first time in the world reported that the skin of patients who have been suffering from psoriasis for 30-55 years and cured, was completely healed without any scars. This is also an important matter to discuss in order to understand the changes occurring in the wounded skin and the way it heals.

IAPs must be administered without delay as well as the methods developed at ROMVAC for the treatment of all psoriasis children and for implementation of a special preventive program concerning potential psoriatic rashes in children, teenagers and adults.

Epidermolysis bullosa (EB) treatment in children

Upon request from a few parents with epidermolysis bullosa children, we administered an oral and topical IAP treatment in 4 children. These treatments are ongoing and we have not been able to determine a final assessment methodology or term yet.

At this point, we can report, for the first time in the world, that the disorders due to the digestive localizations of the disease, from mouth to anus, can be successfully treated in a short time, without knowing for sure what sequelae EB causes in the digestive tube. After administering this IAP treatment, the internal and external wounds on the lips, oral and lingual mucosa, pharynx, esophagus, stomach and intestines have healed and now the children are able to eat normally and they can tolerate any kind of food, including cellulose-containing foods. These children now have a normal intestinal transit. Their health condition has significantly improved during this treatment.

At the same time, the respiratory tract and skin of 9-14 years old children born with EB have improved considerably. A 12 years old female patient with larynx wounds and changed voice, constantly coughing for 7 years and suffering from digestive disorders beginning with lips, tongue, palate, palatine velum and esophagus, received, under strict parental observation, IAPs by aerosols for the respiratory tract, orally for the general treatment and IAP solutions for topical skin treatment. Remarkable health status improvement was reported after 14 days with disappearance of cough, oral and esophageal wounds and normal voice. To this extent, the patient started eating normally and a state of wellbeing could be noticed both in the patient and her parents. Significant improvement was recorded after 30 days, the skin on the soles healed and it became thicker, more flexible and resistant to trauma. During the following weeks, the patient reported that no more blisters had appeared on her skin. The next step is the treatment and specialists will perform clinical examinations to describe each and every part of the body that has been affected by EB.

The small number of patients we have at present forces us to be scientifically cautious and circumspect. But we must make these results available since we are talking about the first children in the world suffering from EB, whose health condition has significantly improved. We are ready to provide information to all special medical institutions in Romania or other countries, and we can also present the entire treatment program including EB patients’ families [16,17].

The most important response is the digestive tube treatment result. A study carried out in Ireland on EB patients from more continents reported that both patients and caregivers wished to firstly solve the digestive tube treatment and, secondly, to find the therapeutical means for pain relief and skin lesions.

 

REFERENCES

  1. Patrascu IV Procedure and installation for the growth of birds free of specific pathogenic germs, OSIM Patent no. 84574/ 108056/7/04/1984, see OSIM Official Monitor 3/1994, p 98; Owner: Romvac Company S.A;
  2. Pătraşcu IV, Chiurciu V, Chiurciu C, Oporanu M, Topilescu G, Mihai I The production and application of PC2 hiperimune egg, OSIM Patent no. A/00810 29.10.2014, see OSIM Official Monitor 5/2015, p 20; Owner: Romvac Company S.A;
  3. Patrascu IV, Tuschak N, Negrutiu T,

Barzoi D, Danalache D, Stoenescu V, Tuschak E The results obtained in the breeding and

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multiplication of a line of birds free of specific pathogenic germs, Rev Zooteh Med Vet, 1969, 12,46-50 (in Romanian);

  1. Patrascu IV, Constantinescu SN, Dublanchet A HIV-1 infection in Romanian children, Lancet, 1990, 335(8690),672;
  1. Pătraşcu IV Evaluation of efficacy of pooled sera in a human immunodeficiency virus antibody prevalence in population surveys,

Rev Roum Virol, 1990, 41(1),45-51;

  1. Cernescu C, Constantinescu SN, Patrascu IV Measles antibodies in HIV-1 infected children, Rev Roum Virol, 41(2),133-134.
  2. Patrascu IV, Dumitrescu O The epidemic of human immunodeficiency virus infection in Romanian children, AIDS Res

Hum Retroviruses, 1993, 9(1),99-104;

  1. Patrascu IV AIDS an Unhealed Wound,

MPM Consult Publ House, 2002, (ISBN 973-85689-6-X) (in Romanian);

  1. Beldescu N, Apetrei R, Calomfirescu A

Nosocomial transmission of HIV in Romania

(Abstract), presented at VIth Intern Conf on AIDS, San Francisco, June 20-24, 1990, published in Conf Vol I, 1990, pp. 159;

  1. Aubin F, Carbonnel F, Wendling D

The complexity of adverse side-effects to biological agents, J Crohn’s Colitis, 2013, 7(4),257–262;

  1. Steenholdt C, Svenson M, Bendtzen K, Thomsen OØ, Brynskov J, Ainsworth MA

Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease.

Aliment Pharmacol Ther, 2011, 34(1),51–58;

  1. Scherer K, Spoerl D, Bircher AJ

Adverse drug reactions to biologics, J Dtsch Dermatol Ges, 2010, 8(6),411–426;

  1. Cassinotti A, Travis S Incidence and clinical significance of immunogenicity to infliximab in Crohn’s disease: a critical systematic review, Inflamm Bowel Dis, 2009, 15(8),1264–1275;
  2. Barbaud A, Granel F, Waton J, Poreaux C How to manage hypersensitivity reactions to biological agents, Eur J Dermatol, 2011, 21(5),667–674;

 

  1. Jones-O’Connor M, McCann A, Kennan A Attitudes to clinical research within the Epidermoloysis Bullsosa (EB) Comunity, Stud Med J, 2015, 2,6-17;
  2. Pătraşcu IV, Chiurciu V, Chiurciu C, Topilescu G Procedure of production and application of chicken immunoglobulin [IgY],

OSIM Patent no. A/00156/25.02.2014, see OSIM Official Monitor 7/2014, p.26; Owner: Romvac Company S.A.;

 

  1. Pătraşcu IV, Chiurciu V, Chiurciu C, Topilescu G Patent nr. A/00179 din

 

  • Correspondance author: Activeimunity, Bdul Dorobanti 1340138, Bl.11.ap 98, Bucharest, Romania, Phone: 0040/745103696, e-mail patrascu_john@yahoo.com

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