Lepromatous leprosy patients produce antibodies that recognise non-bilayer lipid arrangements containing mycolic acids

Baeza, Isabel; Wong-Baeza, Carlos; Valerdi, Esther; Serafín‐López, Jeanet; Ibáñez, Miguel; Estrada‐Parra, Sergio; Wong, Carlos; Estrada-Garcı́a, Iris

doi:10.1590/s0074-02762012000900016

Cited by 17 publications

(9 citation statements)

References 38 publications

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“…Compared to proteins, lipids are deemed rather poorly immunogenic molecules ( 3 ). However, anti-lipid antibodies have been found in patients with infectious diseases, such as leprosy and tuberculosis ( 1 , 10 ), and in patients with autoimmune diseases such as SLE ( 4 ); these antibodies are not only low-affinity IgM, but also high-affinity class-switched IgG antibodies. The cellular mechanisms that lead to the production of these IgM and IgG anti-lipid antibodies have not been elucidated and are poorly studied.…”

Section: Discussionmentioning

confidence: 99%

“…NPA are three-dimensional structures that can emerge when anionic phospholipids with a conical shape, such as phosphatidic acid (PA), phosphatidylserine, or cardiolipin, produced an intermediate form of the tubular hexagonal phase II or inverted micelle that is inserted in a bilayer of lipids (Figure 1 ) ( 6 – 8 ). NPA are transient lipid associations found on the membrane of most cells; when they are stabilized, they can become immunogenic and induce the production of specific antibodies that participate in the pathogenesis of this mouse model of lupus ( 5 , 9 ); moreover, anti-NPA antibodies are found in patients with SLE and leprosy ( 5 , 10 ). On the other hand, liposomes made of a lipid extract from Mycobacterium smegmatis elicit high titers of anti-lipid IgG antibodies, which are cross-reactive with lipid antigens from Mycobacterium tuberculosis ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

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Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Wong-Baeza

Reséndiz-Mora²,

Donis-Maturano

et al. 2016

Front. Immunol.

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Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Wong-Baeza

Reséndiz-Mora²,

Donis-Maturano

et al. 2016

Front. Immunol.

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“…Thus, the need to monitor thrombotic events and anticoagulant among patients with leprosy are still unclear. Baeza et al have identified antibodies to non‐bilayer phospholipid arrangements containing mycolic acids in sera of patients with lepromatous leprosy that contributed to the presence of antiphospholipid antibodies among these patients.…”

Section: Discussionmentioning

confidence: 99%

Lucio phenomenon mimicking antiphospholipid syndrome: The occurrence of antiphospholipid antibodies in a leprosy patient

et al. 2019

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Lucio phenomenon is an atypical reaction of leprosy, characterized by vasculitic lesions that can mimic antiphospholipid syndrome (APS) clinically. Distinguishing the two can be difficult as antiphospholipid autoantibodies may be present in patients with leprosy. We report on a 32‐year‐old female patient presenting with a sudden onset of fever, hemorrhagic bullae, and skin necrosis on her lower legs. She was treated for APS due to the presence of antiphospholipid antibodies but had an inadequate response. A skin biopsy revealed thrombotic vasculopathy and necrotizing vasculitis associated with aggregation of foam cells in the perivascular area and subcutis, with acid‐fast bacilli in the histiocytes and blood vessel walls. Direct immunofluorescence showed IgM, C3, and fibrinogen deposition in the superficial and deep dermal blood vessels. The pathology confirmed the diagnosis of Lucio phenomenon, and appropriate therapy was given. It is essential to evaluate the patient comprehensively, including clinical, serological, and pathological aspects, to obtain the correct diagnosis.

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“…Serological tests are under development but are not used routinely due to their low sensitivity in patients at the tuberculoid pole, and have shown false positive reactions in non-leprosy patients [ 35 ]. Some studies indicate that antibodies specific M. leprae antigens may be useful for detection of early disease in house hold contacts and for monitoring treatment efficacy [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Leprosy in Denmark 1980–2010: a review of 15 cases

2016

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BackgroundLeprosy, caused by Mycobacterium leprae, is a chronic and progressive granulomatous disease affecting mainly the skin and the peripheral nervous system. If left unrecognized, the infection can lead to permanent nerve damage and disability. The clinical presentation depends on the immune response of the patient and can result in a wide spectrum of symptoms. Leprosy is a rare encounter in Scandinavia but remains endemic in some parts of the world, with some areas reporting an increasing incidence. We performed a retrospective record review of leprosy cases in Denmark from 1980 to 2010 with the purpose of presenting the most common geographical, demographic and clinical findings and to discuss the diagnostic and therapeutic challenges of patients with leprosy.Case presentationIn total 15 cases were reviewed. The majority (87 %) of leprosy patients in Denmark were born in South- and Southeast Asia, and were presumed to have contracted the infection in their countries of origin. Patients were predominately young males (mean age: 28.6 years). Anaesthetic skin lesion with or without nerve enlargement were the most common clinical presentations (73 %). Immunological leprosy reactions were seen in 40 % of the cases. Diagnoses were based on clinical findings and skin biopsies. Treatment length varied but all patients received multidrug regimens.ConclusionLeprosy should be kept in mind when encountering patients with suspicious skin lesions originating from leprosy endemic areas or with history of travel or work in the tropics. Due to the long incubation period with symptoms presenting long after immigration or return, clinicians often do not have the diagnosis in mind. The wide spectrum of symptoms and immunological reactions further complicates the diagnostic process. Treatment of leprosy and the complicated immunological reactions, which frequently accompanies the infection, should be performed in collaboration with a specialist.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-015-1768-6) contains supplementary material, which is available to authorized users.

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Lepromatous leprosy patients produce antibodies that recognise non-bilayer lipid arrangements containing mycolic acids

Cited by 17 publications

References 38 publications

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Lucio phenomenon mimicking antiphospholipid syndrome: The occurrence of antiphospholipid antibodies in a leprosy patient

Leprosy in Denmark 1980–2010: a review of 15 cases

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