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Tuberculosis and Allergy

Galina Yakovleva, Yuri Kalambet

Tuberculous nature of glomerulonephritis. This site is devoted to the tuberculosis-induced allergic diseases. The basis of the approach is the Galina Yakovleva own work on treatment of glomerulonephritis as allergic disease. Autoimmune reaction in glomerulonephritis according to this approach is a particular case of infectious allergy. In modern terminology the statement that was proved in the study is that glomerulonephritis is caused by Latent tuberculosis infection (LTBI).
The study was performed in 60s of the 20th century and the essence was as follows. 72 people, ill with glomerulonephritis (no active TB cases), were tested with 5 allergens of most important infections: hemolitic streptococcus, alpha-hemolytic streptococcus, hemolitic staphylococcus, brucellosis and tuberculosis. Only tuberculine skin tests (TST) induced general and specific reaction of the patients (increased temperature, increased concentration of protein and blood cells in urine after 48 hours). Anti-TB treatment of 22 most serious cases of glomerulonephritis gave very good results. Streptococcus infection that is commonly considered as a trigger, causing glomerulonephritis, can be treated as a release factor for tuberculosis infection rather than the direct reason of the glomerulonephritis. The author considers LTBI as the most probable reason that induced glomerulonephritis. This conclusion was independently supported by experiments with guinea pigs in 1970s [1].

Micobacterium tuberculosis (M.tuberculosis, Mtb) – companion of the mankind, walking together with humans for several thousand years. Can get along with man, cattle, pets, rodents, and even with fish. More than 90% of human population are carriers of MTb infection both in developing and developed counties. About 5% of population never show positive TST.  Maybe, they will never be ill with Tuberculosis. Disease rate in regions, where people seldom (or never) meet tuberculosis is about 0.5% per year. In wealthy countries it is 100 times lower. In Russia – 10 times lower. Wealthy countries are Europe and North America. Pandemia of tuberculosis could be less pronounced in Russia due to its (Russia) size. Some of hypersensitive to MTb population could be left untouched by MTb.

Diversity: Many types, most deeply investigated – M.tuberculosis, M.bovis and Bacillus Calmette–Guérin (BCG). M.Tuberculosis is used also as a name of the whole family. Classic acid-fast bacillus found by Koch is just one of its forms. In the case of adverse conditions of growth it can easily lose its cell wall and convert into so-called L-form [1–3]. L-form is non-acid-fast coccobacilli, some of them can revert to classic MTb. In the clinically healthy human organism MTB mostly persist in L-form[1] as a latent tuberculosis infection. BSG vaccine in the children also converts to L-form in one-two years. L-forms grow much faster, than classic MTb[1,2]. In clinical practice latent tuberculosis infection (LTBI) is not treated as tuberculosis disease, whereas guinea pigs, infected by L-forms, show symptoms of endovasculitis and glomerulonephritis [1]. The cause of glomerulonephritis was shown to be tuberculous [4].

Famous relatives: M.Leprae, the causative agent of leprosy

Vaccination: by infecting human with bacillus Calmette-Guerin (BCG) has limited effect. Some of countries make vaccination of all children at birth. BCG is derived from M.Bovis. BCG differs from M.Boves by one big deletion, coding a couple of proteins: ESAT-6 and CFP-10[5]. The proteins are secretory and are used for lysis of the host (e.g. macrophage) cell. They are never included in Mtb cell wall or membrane. Immune reaction of human to these protein is just a side-effect, and has nothing to do with the fight of immune system against tuberculosis. Besides, this reaction successfully indicates active state of very dangerous mechanism of proliferation of Mtb.

Test for infection: tuberculine skin/sensitivity test (TST), another name – Mantoux test. TST causes neuro-humoral reaction to combination of Mtb proteins. Positive reaction indicates, that the organism is infected with some form of Mtb. As already mentioned, more than 90% of adults are infected with Mtb.

Test for active intracellular proliferation: Interferon-γ release assay (IGRA), Diaskintest in Russia. Both tests detect antibodies to ESAT-6 and CFP-10 proteins. Positive test means, that intracellular proliferation of Mtb is or recently was active and hence it is not BCG. 30% of clinically ill people have negative Diaskintest.

References:

[1]        Z.S. Zemskova, I.. Dorozhkova, Latent tuberculosis infection (in Russian), Meditsina, Moscow, 1984.

[2]        N. Markova, G. Slavchev, L. Michailova, Unique biological properties of Mycobacterium tuberculosis L-form variants: Impact for survival under stress, Int. Microbiol. 15 (2012) 61–68. doi:10.2436/20.1501.01.159.

[3]        N. Markova, G. Slavchev, L. Djerov, A. Nikolov, T. Dimova, Mycobacterial L-forms are found in cord blood: A potential vertical transmission of BCG from vaccinated mothers, Hum. Vaccines Immunother. 12 (2016) 2565–2571. doi:10.1080/21645515.2016.1193658.

[4]        G. Iakovleva, Paratuberculous nephritis (in Russian), Klin. Med. (Mosk). 80 (2002) 37–43.

[5]        J.D. Ernst, G. Trevejo-nuñez, N. Banaiee, Science in medicine Genomics and the evolution , pathogenesis , and diagnosis of tuberculosis, J. Clin. Invest. 117 (2007) 1738–1745. doi:10.1172/JCI31810.1738.