Granulomatous Hypersensitivity Research Articles

A Case of Granulomatous Hypersensitivity Reactions to a Dermal Filler Precipitated by PD-1 Checkpoint Inhibitor Therapy

Injection of filler material has become routine in dermatology in improving the appearance of rhytides and increasing skin volume associated with aging. While the vast majority of injections are accomplished without complications, foreign body reactions may develop in a certain percentage of individuals. We recently encountered a 65-year-old woman with recurrent malignant melanoma who presented with marked thickening along the sides of her face for approximately 2 months. She recently received nivolumab infusions for recurrent malignant melanoma and noted that symptoms worsened after each infusion. She reported having had cosmetic procedures done three years prior, one of which was an injection of a long-lasting dermal filler, polymethylmethacrylate microsphere enhanced bovine collagen (Bellafill). A biopsy of two areas revealed nodular infiltrates of histiocytes with small round lobules recognizable as polymethylmethacrylate microspheres. Based on clinical and histopathologic findings, a diagnosis of granulomatous dermatitis filler reaction was rendered. Nivolumab is a PD-1 checkpoint inhibitor that disrupts T-cell inhibitory pathways leading to increased immune activation. In this case, the immune activation triggered a florid granulomatous reaction to the filler the patient had been injected with 3 years previously. We present this case as the second report of this phenomenon and the first in the dermatologic literature. This is a newly recognized side effect of PD-1 checkpoint immunotherapy and patients who are about to initiate such therapy who have had filler injections should be warned about this potential complication.

16622 Granulomatous reaction to microneedling

A 49-year-old Caucasian female with a history of type two diabetes mellitus and essential hypertension presented for outpatient evaluation for pruritic tender erythematous scaling plaques on the face that arose abruptly 7 days after a microneedling session to the corresponding areas. The microneedling was performed in a medical spa and a hyaluronic acid, glycerin, zinc, and copper containing serum was applied before the treatment session. The patient had minimal relief of symptoms with BID application of triamcinolone acetonide 0.1% cream for 7 weeks that was prescribed by per primary care provider. The patient denied any systemic symptoms. A 4-mm punch biopsy was performed and the patient was initiated on minocycline 100 mg bid orally, clobetasol 0.05% cream bid × 7 days followed by triamcinolone acetonide 0.1% cream bid × 7 days, then iodoquinol 1%-hydrocortisone 1% cream bid × 7 days, then tacrolimus 0.1% ointment bid. The punch biopsy revealed a granulomatous dermatitis with no foreign body observed with polarized light. Systemic and cutaneous sarcoidosis and infectious etiologies were ruled out before a diagnosis of granulomatous reaction to microneedling was reached. Traditionally, granulomatous hypersensitivity reactions have followed inoculation of metallic elements, silica, zirconium or collagen. Granulomatous hypersensitivity reactions secondary to dermal inoculation of antigenic cosmeceutical products during microneedling is likely severely underreported. The majority of products applied before microneedling sessions are not FDA approved for intradermal injection. This case hopes to bring awareness to adverse reactions to microneedling.

Regulation of Liver Fibrosis during Murine Schistosomiasis Mansoni

Background: The main pathology of Schistosoma mansoni (S. mansoni) infection is induced by a granulomatous tissue reaction against the parasite eggs. Unfortunately, no therapy has been proven to prevent the progression of hepatic fibrosis associated with granulomatous hypersensitivity to parasite eggs. Accumulating evidence has demonstrated a critical pathogenic role for both interleukin 17 (IL-17) and interleukin 13 (IL-13) in organ fibrosis. Objective: The present study investigated the role of IL-17 and IL-13 in the pathogenesis of liver fibrosis during S. mansoni infection. Material and Methods: Thirty female C57BL/6 mice were divided into three groups, normal, infected, and anti- mouse IL-17 treated groups. The infected and anti-mouse IL-17 groups were infected with 40±5 cercariae of S. mansoni per mouse. Neutralizing rat anti-mouse IL-17 mAb or an isotype-matched rat IgG mAb was first administered intraperitoneally 3 weeks after S. mansoni infection (62.5μg per mouse) then at the same dose every third day until 2 days before killing. Serum IL-17, IL-13, and proinflammatory cytokines levels were determined by ELISA. Liver granulomas were measured by an ocular micrometer. Results: Serum level of IL-17 was significantly higher in infected mice compared with non-infected animals. Reducing IL-17 activity using anti-IL-17 monoclonal antibodies improves liver functions and reduces the size of the liver granulomas. Meanwhile, Th-2 profibrogenic cytokine IL-13 was also decreased in infected/anti-IL-17 mAB- treated mice. IL-17-induced proinflammatory mediators (IL-1Land TNF-that involved in liver fibrosis were markedly reduced in anti-IL-17 mAB-treated mice. Conclusion: IL-17 and IL-13 contribute to granulomatous inflammatory and fibrosing reactions in murine schistosomiasis.

Regulation of Liver Fibrosis during Murine Schistosomiasis Mansoni

Background: The main pathology of Schistosoma mansoni (S. mansoni) infection is induced by a granulomatous tissue reaction against the parasite eggs. Unfortunately, no therapy has been proven to prevent the progression of hepatic fibrosis associated with granulomatous hypersensitivity to parasite eggs. Accumulating evidence has demonstrated a critical pathogenic role for both interleukin 17 (IL-17) and interleukin 13 (IL-13) in organ fibrosis. Objective: The present study investigated the role of IL-17 and IL-13 in the pathogenesis of liver fibrosis during S. mansoni infection. Material and Methods: Thirty female C57BL/6 mice were divided into three groups, normal, infected, and anti- mouse IL-17 treated groups. The infected and anti-mouse IL-17 groups were infected with 40±5 cercariae of S. mansoni per mouse. Neutralizing rat anti-mouse IL-17 mAb or an isotype-matched rat IgG mAb was first administered intraperitoneally 3 weeks after S. mansoni infection (62.5μg per mouse) then at the same dose every third day until 2 days before killing. Serum IL-17, IL-13, and proinflammatory cytokines levels were determined by ELISA. Liver granulomas were measured by an ocular micrometer. Results: Serum level of IL-17 was significantly higher in infected mice compared with non-infected animals. Reducing IL-17 activity using anti-IL-17 monoclonal antibodies improves liver functions and reduces the size of the liver granulomas. Meanwhile, Th-2 profibrogenic cytokine IL-13 was also decreased in infected/anti-IL-17 mAB- treated mice. IL-17-induced proinflammatory mediators (IL-1Land TNF-that involved in liver fibrosis were markedly reduced in anti-IL-17 mAB-treated mice. Conclusion: IL-17 and IL-13 contribute to granulomatous inflammatory and fibrosing reactions in murine schistosomiasis.

A skin test for latent tuberculosis

To the Editor: Penn-Nicholson et al.[1] have suggested using a blood test for diagnosing early tuberculosis. It may be possible, however, to use a skin test to diagnose latent tuberculosis.[2,3] An autoimmune model of tuberculoid leprosy has been developed, using peripheral nerve as antigen. Rabbits were injected with a homogenate of human sensory nerve plus adjuvant. Some of the rabbits developed a state of granulomatous hypersensitivity; i.e. skin testing with a dilute solution of nerve in saline produced an epithelioid cell granuloma, in which the cytoplasm contained dilated rough endoplasmic reticulum filled with an electron-dense product.[4] The antigen is a non-myelin protein, active in doses of 1 μg. The ultrastructural appearances are similar to those in human tuberculoid leprosy. [5]

Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation.

Developing efficient protocols for synthesis, antiosteoarthritic, antiinflammatory assessments and docking studies of nitrogen-containing bisphosphonate derivatives

We report herein, two synthetic approaches to three types of nitrogen-containing bisphosphonates (N-BPs) in moderate to high yields (58–88%). Ester cleavage of selected bisphosphonates was undertaken to obtain their N-BP-acid analogs. Based on the reported bisphosphonate properties and the prospective biological prediction using computer-assisted molecular modeling (CAMM), new compounds were evaluated in a mouse model of antigen-induced arthritis (AIA) and the delayed-type hypersensitivity granuloma reaction (DTH-GRA) for chronic inflammation. Pharmacological results showed that N-BP-acids are more favorable for antiarthritis activity than N-BP-esters. On the other hand, the majority of N-BPs revealed good antiinflammatory potency compared to their acid analogs. The results also showed that the presence of a free thiol group in a molecule enhances the anti-inflammatory activity. Furthermore, bioscreening results were in good agreement with the prediction investigation. A hypothesis of molecular modeling study, including fitting of the synthesized compounds into 3D-pharmacophore using Discovery Studio 2.5 software and their docking into the human farnesyl pyrophosphate synthase (hFPPS, PDB code: 2F8C protein) showed good results consistent with the observed pharmacological properties.

Granulomatous tattoo reaction in a young man

In September, 2012, a 37-year-old man attended our clinic a month after noticing the appearance of small erythematous papules underlying a 12-year-old tattoo on his right leg. He also complained of progressive muscle ache in both his legs. 2 weeks before coming to the clinic, he started having pain and swelling of both ankles, and also noticed fever, fatigue, and night sweats. Physical examination showed swelling of both ankles and erythema over the Achilles tendon; the area was very tender to palpation and the patient had limited range of motion. Over the lateral aspect of the right leg there was an ovoid blue to grey tattoo; within the areas of tattoo ink were scattered well-demarcated pink papules and plaques with overlying white scale (fi gure). Laboratory investigations showed normochromic, normo cytic anemia, erythrocyte sedimentation rate of 105 mm/h, raised 1,25-dihydroxivitamin D, normal calcium and angiotensin converting enzyme concentrations, and HIV serology was not reactive. Chest radiography showed bilateral linear opacities and hilar adenopathies. Tuberculin skin test was not done because of previously treated latent tuberculosis infection 10 years ago. Reactive arthritis was suspected but the patient did not report multiple sexual partners or urinary symptoms. Urinary DNA analysis for chlamydia and gonococcus was negative. Rheumatological blood tests were normal, and blood cultures were negative. Chest CT scan was done and showed hilar and subcarinal adenopathies. A punch biopsy of the lesion over the tattoo was done: it showed non-caseating granulomas compatible with sarcoidosis (fi gure). The diff erent stains in the biopsy specimen were negative for infectious agents. Ophthalmological assessment was unremarkable. The patient was started on oral prednisone and showed striking improvement within a few days. He was discharged, and at last follow-up in January, 2013, he was symptom free. Prednisone had been tapered off at that time. Skin involvement in sarcoidosis occurs in 20–35% of cases, usually in early stages of the disease, providing a valuable opportunity for timely diagnosis. The fi rst report that related tattoos to systemic sarcoidosis was published in 1955, and 32 reports in total were published before 2012. Sarcoid lesions usually occur in the red (cinnabar), black (ferric oxide), and blue-black areas of tattoos. The age of the tattoo before sarcoidal manifestations is widely variable and ranges from months to decades. Chronic low-grade exposure of the immune system to an antigen substance in the foreign material might ultimately lead to systematised granulo matous hypersensitivity. The association of new-onset pronounced ankle arthritis and bilateral hilar lymphadenopathy without erythema nodosum, especially in men, has been suggested as a variant of Lofgren’s syndrome, and this pattern of ill ness has an excellent prognosis. Tattoo sarcoidosis, as described in our patient, could be the fi rst manifestation of sarcoidosis. The importance of skin biopsy during the initial assessment should be remem bered, and this clinical presentation should alert the clinician to an early diagnosis.

Synthesis, Quantitative Structure–Activity Relationship, and Anti-Inflammatory Profiles of Substituted 5- and 6-N-Heterocycle Bisphosphonate Esters

A modified multicomponent reaction in a one-pot synthesis of a new series of substituted N-heterocyclic aminomethylene bisphosphonates, in high rates, was described. Accordingly, synthesis of α-aminobisphosphonates was achieved, via the Kabachnik–Fields reaction, from the substituted amine with triethyl orthoformate, and followed by treating the product mixture with a toluene solution containing diethyl phosphite–sodium salt. The design of potentially anti-inflammatory bisphosphonates (BPs) relied on the results of computer-assisted molecular modeling. If Later, new BPs were evaluated in animal model of chronic inflammation using the delayed-type hypersensitivity granuloma reaction.

Immunization with rP22 induces protective immunity against Schistosoma mansoni: Effects on granuloma down-modulation and cytokine production

Schistosomiasis remains a significant public health problem in tropical countries and it is recognized as the most important human helminth infection in terms of morbidity and mortality. Although the existing antischistosomal drugs are highly effective, they do not prevent against reinfection or granuloma formation. Therefore, vaccine strategies are essential for the control of schistosomiasis. Our group recently identified the recombinant (r) P22 protein, a component of the adult worm protein fraction PIII that has been shown to engender protective and immunomodulatory effects on murine schistosomiasis. A cDNA clone encoding rP22 was isolated from a Schistosoma mansoni adult worm cDNA library using anti-PIII rabbit serum; it exhibited complete identity with S. mansoni Sm21.7 EF-hand antigen. Confocal microscopy revealed that rP22 is a tegument protein localized on the surface of S. mansoni miracidia and adult worms. Mice immunized with rP22 exhibited a 51% and 22.5% decrease in adult worm burden and in hepatic eggs, respectively. Additionally, rP22 vaccine produced a reduction in 60% of liver granuloma size and 71% of fibrosis in mice, suggesting that rP22 might contribute to down-modulate granulomatous hypersensitivity to S. mansoni eggs. Protective immunity in mice was associated with high titers of rP22-specific IgG antibodies; elevated production of IFN-γ, TNF-α and IL-10; and a reduced level of IL-4. In conclusion, these findings indicate that rP22-based vaccines could be useful to elicit protection and reduce pathology associated to schistosomiasis.

Experimental leprosy: a model of epithelioid cell granuloma

An animal model of granulomatous hypersensitivity has been developed, which reproduces some features of the pathologies of important chronic granulomatous disorders, including tuberculosis, tuberculoid leprosy, sarcoidosis, berylliosis, Crohn's disease, and sensitivity to zirconium. The lesions consist of focal collections of epithelioid cells surrounded by lymphocytes to form tubercles. The epithelioid cell has a secretory function and is not phagocytic. Plasmacytoid dendritic cells are precursors of epithelioid cells, which are therefore part of the innate immune system. Subplasmalemmal linear densities are also present in these cells. This autoimmune model has been induced in rabbits using a non-myelin sensory peripheral antigen to reproduce the features of tuberculoid leprosy. The antigen is probably present only in human tissue. A granuloma antigen, which is tissue specific similar to that in peripheral nerves, could be present in sarcoidosis and Crohn's disease. In multiple sclerosis, mononuclear cells in the brain parenchyma are not phagocytic and are therefore similar to epithelioid cells. The induction of tolerance leading to the development of a vaccine to prevent the lesions in multiple sclerosis, sarcoidosis, and Crohn's disease is possible after purification of the granuloma antigen.

Foreign Body or Hypersensitivity Granuloma of the Inner Ear After Cochlear Implantation: One Possible Cause of a Soft Failure?

A tissue response in the form of foreign body or a hypersensitivity reaction to cochlear implantation is common and may be one possible cause of a soft failure of cochlear implantation. After a successful cochlear implantation, delayed failure may occur. The causes of a "soft" failure, that is, one in which device malfunction cannot be proven, are unknown. The histopathology of the temporal bones of a patient who, in life, had experienced a soft failure after cochlear implantation was described. In addition, the temporal bones of 8 other subjects who, in life, had undergone cochlear implantation were studied for evidence of a foreign body or hypersensitivity reaction. In the case report, a necrotizing granulomatous giant cell reaction surrounded the cochlear implant electrode track through the mastoid and the middle ear and into the cochlea in both ears. There was osteolysis of the cribrose area, otic capsule, and bone between the facial nerve and the cochlea and destruction of the organ of Corti and spiral ganglion. In the additional 8 cases studied, a similar, although less pronounced, foreign body or hypersensitivity reaction was seen in 6 (75%) of the cases. A foreign body or hypersensitivity reaction in the form of giant cells and lymphocytic cell infiltration is common after cochlear implantation and may be one possible cause of soft failure.

Mycobacterial trehalose 6,6′-dimycolate preferentially induces type 1 helper T cell responses through signal transducer and activator of transcription 4 protein

Mycobacterium tuberculosis is an intracellular pathogen of tuberculosis and its pathogenicity is related to the ability to escape killing by ingested macrophages and induce delayed-type hypersensitivity (DTH). A major component of the cell wall of M. tuberculosis is trehalose 6,6′-dimycolate (TDM), which has been implicated as a pathogenetic factor. The expression of DTH and cell-mediated immunity is dependent on the macrophage-cytokine-type 1 helper T (Th1) lymphocyte axis. Cytokines, interleukin-12 (IL-12) and interferon-γ (IFN-γ), play a critical role in the process and IL-12-activated signal transducer and activator of transcription (STAT) 4 is required for the development of fully functional Th1 cells. To clarify host responses to mycobacterial TDM, we have analyzed footpad reaction, histopathology and cytokine profile of experimental granulomatous lesions using STAT4-deficient mice. In the present study, we have demonstrated that mycobacterial TDM selectively induces the Th1 response through the STAT4 signaling pathway, because mice lacking STAT4 protein significantly reduced to develop DTH, hypersensitivity granulomas, and Th1 cytokine responses, when compared to BALB/c mice. These results shed light on the molecular pathogenesis of mycobacterial disease. Taken together with previous studies, TDM is a pleiotropic molecule against the host and participates in the pathogenesis.

Schistosoma mansoni PIII antigen modulates in vitro granuloma formation by regulating CD28, CTLA-4, and CD86 expression in humans

We investigated the in vitro responses of peripheral blood mononuclear cells (PBMC) from intestinal chronic schistosomiasis patients to PIII, a multivalent antigen prepared from Schistosoma mansoni adult worm. PIII decreased cellular proliferation and granulomatous reaction. Moreover, induced the reduction of IFN-γ levels and increased IL-10 production. To better understand the mechanism through which the observed suppression occurs, the present study focused on the phenotypic pattern displayed by PBMC treated with PIII in an in vitro granuloma assay. Expression of the surface markers CD28, CTLA-4 and CD86 by lymphocytes and monocytes were analyzed by flow cytometry. Our results demonstrated a significant decrease of CD28+CD4+ and CD28+CD8+ T-cell percentage stimulated by PIII compared to its non-infected counterparts. This suppressive effect was related to a significant increase in the percentage of T-cells expressing CTLA-4. PIII also promoted a significant increase in the percentage of cells expressing CD86. Indeed, our results demonstrated that PIII was capable of modulating in vitro granuloma reaction, and this event was related to the balance of IL-10, IFN-γ and CD28, CTLA-4, CD86 bringing new insight to the immunoregulation of granulomatous hypersensitivity in human schistosomiasis.

Modulation of granulomatous hypersensitivity against Schistosoma mansoni eggs in mice vaccinated with culture-derived macrophages loaded with PIII

Granuloma modulation induced by antigen is an attractive model for vaccination studies of experimental schistosomiasis to test the effect of anti-pathology vaccine. We describe here an immunization procedure with culture derived macrophages-pulsed PIII, a known anionic antigen purified from S. mansoni adult worm, involved in the inhibition of granulomatous response to eggs. For our studies, peritoneal or spleen macrophages cultured over 15 days were loaded with PIII. Both macrophage sub-populations were capable to efficiently take up and subsequently present PIII to lymphocytes as evidenced by immunofluorescence assay. The vaccination of mice with intravenous injection of PIII-loaded macrophages potently induced antigen-specific immune response to S. mansoni antigens as determined by cell proliferation assay. This immunization procedure of mice caused significant decrease in hepatic granuloma formation and in vitro granuloma reaction to S. mansoni antigens coupled to polyacrylamide beads (PB-SEA, PB-SWAP or PB-PIII). Assessment of in vitro granuloma supernatant of spleen cells from PIII-loaded macrophages vaccinated mice revealed significant amounts of Th1-cytokines IFN-γ and IL-2 compared to control cells. Collectively, our results indicate that culture derived-macrophages provided a valuable research tool to investigate aspects of immune response that promote modulation of granulomatous hypersensitivity to S. mansoni eggs in mice.

The role of IL-10 and IgG1 in the protection and granulomatous response in Schistosomamansoni P24-immunized mice

Previous work by our laboratory identified a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, designated PIII, able to elicit significant in vitro cell proliferation, and lower in vitro and in vivo granuloma formation. In the present work, we investigated some biological activities of P24, an antigenic component of PIII. Immunization of mice with this antigen induced a significant protection degree against challenge infection and significant decrease in the hepatic granuloma formation. Pre-incubation of spleen cells from P24-immunized mice with S. mansoni antigens induced a significant increase of interleukin (IL)-10 levels, but not interferon-γ, in the cell supernatants. In addition, mice immunized with different S. mansoni antigens and P24 displayed indistinguishable levels of IgG2a in response to anti- S. mansoni antigens, while IgG1 levels were significantly increased. Collectively, our results indicate that P24 might mediate protective anti-parasite immunity and downregulate granulomatous hypersensitivity to S. mansoni eggs in part by its ability to induce a higher production of IgG1 and IL-10.

Genetic polymorphism and clinical outcome: identification of individuals at risk of a poor clinical outcome.

Susceptibility and outcome in complex disorders such as asthma and cancer appear to be determined, at least in part, by genetic polymorphism. However, while our ability to identify new allelic variants and study them in case and control populations has greatly improved, considerable difficulties remain in elucidating how many genes determine particular clinical phenotypes. This is because most studies have concentrated on study of single genes in relatively small study groups. The important issues of gene-gene interactions (epistasis) and high-risk subgroups have not yet been adequately addressed. We now describe a general approach, using patients with head and neck cancers as an example. Our purpose is to demonstrate candidate gene selection, statistical approaches, and identification of patient subgroups.

Expression and Participation of Eotaxin During Mycobacterial (Type 1) and Schistosomal (Type 2) Antigen-Elicited Granuloma Formation

Eotaxin participation was analyzed during types 1 and 2 lung granuloma formation induced by embolizing Sepharose beads coupled to purified protein derivative (PPD) of Mycobacterium bovis or soluble Ags derived from Schistosoma mansoni eggs. Eotaxin was monitored by protein ELISA and semiquantitative reverse-transcriptase PCR mRNA analysis. Both types 1 and 2 granulomas released eotaxin, but levels were sixfold greater (on day 4) in the type 2 than for the type 1 or foreign body granulomas. Transcripts for eotaxin, IL-4, and CCR3 (eotaxin receptor) were also enhanced during type 2 granuloma formation. Anti-IL-4 treatment impaired eotaxin mRNA in lungs with type 2 granulomas, indicating that IL-4 promoted local eotaxin expression. In vivo, anti-eotaxin treatment caused modest reductions in the size of both types 1 and 2 lesions, with negligible effect on eosinophil recruitment. Surprisingly, anti-eotaxin treatment abrogated IFN-gamma-producing cells in regional lymph nodes during the type 1 PPD response. Lymph nodes draining both types 1 and 2 lesions showed enhanced CCR3 mRNA, but this followed the time of maximum eotaxin protein and mRNA expression. Correlative, in vitro studies revealed that graded doses of eotaxin increased IFN-gamma production from PPD-sensitive regional lymph node cultures, while monocyte-chemotactic protein-1, an important macrophage chemoattractant, had the opposite effect. These findings indicate that eotaxin expression is not limited to type 2 hypersensitivity granulomas, but also promotes IFN-gamma production during mycobacterial responses.

Induction of protective immunity against Schistosoma mansoni infection by antigens purified from PIII, a fraction of adult worm, associated to the downregulation of granuloma formation.

This study was performed in order to define Schistosoma mansoni antigens able to function as modulator agents in BALB/c mice granulomatous hypersensitivity to parasite egg. The antigens P-24, P-35 and P-97 were purified by affinity chromatography from a fraction of S. mansoni adult worm antigenic preparation, denominated PIII, involved in the inhibition of granulomatous response to eggs. Immunization of mice with these antigens, in the presence of Corynebacterium parvum and Al(OH)3 as adjuvant, induced a significant protection degree against challenge infection, as observed by the decrease on worm burden recovered from portal system. In vitro blastogenesis assays revealed that purified antigens were able to induce significant proliferation of spleen cells from S. mansoni-infected mice. This protection was correlated to significant decrease in granuloma size induced by PIII. From these results, we concluded that PIII preparation contains antigens capable of mediating protective anti-parasite immunity and down-regulating granulomatous hypersensitivity to S. mansoni eggs.

Evidentiation of paramyosin (Sm-97) as a modulating antigen on granulomatous hypersensitivity to Schistosoma mansoni eggs.

A Schistosoma mansoni adult worm anionic fraction (PIII) has previously been shown to protect mice against challenge infection and to reduce pulmonary and hepatic granulomatous hypersensitivity. Serum from PIII-immunized rabbit was used to screen a lambda gt11 cDNA library from S. mansoni adult worm in order to identify antigens capable of modulating granulomatous hypersensitivity. We obtained four clones with 400 (Sm-III.11), 900 (Sm-III.16), 1100 (Sm-III.10) and 1300 (Sm-III.12) bp of length. All clone-specific antibodies were able to recognize most of the PIII components. The sequence analysis showed that these clones presented high homology with S. mansoni paramyosin (Sm-97). These findings ascribe a new function to this antigen with an important role in modulation of granulomatous hypersensitivity to S. mansoni eggs.