Polyclonally Derived Alloantigen-Specific T Regulatory Cells Exhibit Target-Specific Suppression and Capture MHC Class II from Dendritic Cells.

Foxp3+ T regulatory (Treg) cells prevent allograft rejection and graft-versus-host disease. Although polyclonal Tregs have been used both in animal models and in humans, the fine specificity of their suppressive function is poorly defined. We have generated mouse recipient-derived alloantigen-specific Tregs in vitro and explored the fine specificity of their suppressive function and their mechanism of action in vitro and in vivo. In vitro, when alloantigen and peptide Ag were both presented on the same dendritic cell, both responses were suppressed by iTregs specific either for the alloantigen or for the peptide Ag. In vivo, iTreg suppression was limited to the cognate Ag, and no bystander suppression was observed when both allo-antigen and peptide Ag were present on the same dendritic cell. In vitro, alloantigen-specific Tregs captured cognate MHC but failed to capture noncognate MHC. Our results demonstrate that a polyclonal population of iTregs generated from naive T cells can mediate highly specific function in vivo and support the view that Treg therapy, even with unselected polyclonal populations, is likely to be target antigen-specific and that bystander responses to self-antigens or to infectious agents are unlikely.

Lymphocyte subset analysis in QuantiFERON-TB Gold Plus and T-Spot.TB for latent tuberculosis infection in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an immune mediated inflammatory disorder, and immune suppressive drugs are prescribed. RA patients receiving treatments are in a kind of immunosuppressive condition that presents increased risk of developing active tuberculosis. Accurate diagnosis of latent tuberculosis infection (LTBI) is recommended for RA. QuantiFERON®-TB Gold Plus (QFT-Plus), a novel IGRA, has two tubes (TB1 and TB2). TB2 is designed to elicit both CD4 and CD8 T-cell responses, with expected increased sensitivity. We conducted a cross-sectional study to compare two IGRAs, QFT-Plus and T-SPOT®.TB (TSPOT), in RA. One hundred fifty-two RA patients (median age: 66.5 yrs) were enrolled. QFT-Plus and TSPOT were concurrently conducted. Lymphocyte subsets (CD4 T-cell and CD8 T-cell) were also measured. The positivity rates of QFT-Plus and TSPOT were 9.7% and 4.5%, respectively, with the difference being significant (P < 0.01). The positivity rates in TB1 and TB2 were 9.1% and 7.1%, respectively; the difference was not significant (P = 0.18). Patients with CD4 T-cell ≥650/µL and CD8 T-cell ≥400/µL had significantly higher positivity rates in both QFT-Plus and TSPOT in comparison with other groups (P < 0.01 and P < 0.05, respectively). QFT-plus demonstrated a higher positivity rate than TSPOT. However, there was little additional effect for detecting LTBI by TB2. Lymphocyte subsets were strongly associated with immune response in both QFT-Plus and TSPOT. LTBI should not be ruled out even with a negative IGRA result in patients with CD4 T-cell <650/µL or CD8 T-cell <400/µL.

Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice.

BACKGROUND: Patients with house dust mite (HDM) allergy or Ascariasis produce serum IgE specific to the antigens of HDM or nematode Ascaris, respectively. Although human IgE cross-reactivity has been reported between HDM and Ascaris antigens, it remains unclear whether it contributes to the pathogenesis of allergic diseases. We herein investigated the induction of cross-reactive antibodies and T cells in mice and effects of airway exposure to HDM antigens after preimmunization with Ascaris antigens. METHODS: Mice were intraperitoneally immunized with HDM or Ascaris antigens with Alum, followed by the intranasal administration of HDM antigens. Serum antigen-specific IgE and IgG were measured by ELISA. Cytokine release in splenocytes from Ascaris-immunized mice upon in vitro restimulation with HDM antigens were measured by ELISA. RESULTS: Immunization with Ascaris or HDM antigens induced cross-reactive IgG1. Splenocytes from Ascaris-immunized mice released IL-5 and IL-13 in response to the restimulation with HDM antigens. Subsequent airway exposure to HDM antigens promoted the induction of HDM-specific IgE and upregulation of HDM-specific IgG1 in Ascaris-immunized mice, whereas these responses were not detected or smaller without the Ascaris presensitization. CONCLUSIONS: We demonstrated that the immunization of naïve mice with Ascaris antigens induced production of antibodies and differentiation of Th2 cells, which were cross-reactive to HDM antigens, and accelerated induction of serum HDM-specific IgE upon subsequent airway exposure to HDM antigens in mice. These results suggest that sensitization to HDM towards IgE-mediated allergic diseases is faster in individuals with a previous history of Ascaris infection than in those without presensitization to Ascaris.

Targeting ROCK2 improves macromolecular permeability in a 3D fibrotic pancreatic cancer microenvironment model.

Pancreatic cancer is characterized by a densely fibrotic stroma. The fibrotic stroma hinders the intratumoral penetration of nanomedicine and diminishes therapeutic efficacy. Fibrosis is characterized by an abnormal organization of extracellular matrix (ECM) components, namely the abnormal deposition and/or orientation of collagen and fibronectin. Abnormal ECM organization is chiefly driven by pathological signaling in pancreatic stellate cells (PSCs), the main cell type involved in fibrogenesis. However, whether targeting signaling pathways involved in abnormal ECM organization improves the intratumoral penetration of nanomedicines is unknown. Here, we show that targeting transforming growth factor-ß (TGFß)/Rho-associated kinase (ROCK) 1/2 signaling in PSCs normalizes ECM organization and concomitantly improves macromolecular permeability of the fibrotic stroma. Using a 3-dimensional cell culture model of the fibrotic pancreatic cancer microenvironment, we found that pharmacological inhibition of TGFß or ROCK1/2 improves the permeation of various macromolecules. By using an isoform-specific pharmacological inhibitor and siRNAs, we show that targeting ROCK2, but not ROCK1, alone is sufficient to normalize ECM organization and improve macromolecular permeability. Moreover, we found that ROCK2 inhibition/knockdown attenuates Yes-associated protein (YAP) nuclear localization in fibroblasts co-cultured with pancreatic cancer cells in 3D. Finally, pharmacological inhibition or siRNA-mediated knockdown of YAP normalized ECM organization and improved macromolecular permeability. Our results together suggest that the TGFß/ROCK2/YAP signaling axis may be therapeutically targeted to normalize ECM organization and improve macromolecular permeability to augment therapeutic efficacy of nanomedicines in pancreatic cancer.

Retinal regeneration after injury induced by gamma-ray irradiation during early embryogenesis in medaka, Oryzias latipes.

PURPOSE: Zebrafish, a small fish model, exhibits a multipotent ability for retinal regeneration after damage throughout its lifetime. Compared with zebrafish, birds and mammals exhibit such a regenerative capacity only during the embryonic period, and this capacity decreases with age. In medaka, another small fish model that has also been used extensively in biological research, the retina's inner nuclear layer (INL) failed to regenerate after injury in the hatchling at eight days postfertilization (dpf). We characterized the regenerative process of the embryonic retina when the retinal injury occurred during the early embryonic period in medaka. METHODS: We employed a 10 Gy dose of gamma-ray irradiation to initiate retinal injury in medaka embryos at 3 dpf and performed histopathological analyses up to 21 dpf. RESULTS: One day after irradiation, numerous apoptotic neurons were observed in the INL; however, these neurons were rarely observed in the ciliary marginal zone and the photoreceptor layer. Numerous pyknotic cells were clustered in the irradiated retina until two days after irradiation. These disappeared four days after irradiation, but the abnormal bridging structures between the INL and ganglion cell layer (GCL) were present until 11 days after irradiation, and the neural layers were completely regenerated 18 days after irradiation. After gamma-ray irradiation, the spindle-like Müller glial cells in the INL became rounder but did not lose their ability to express SOX2. CONCLUSIONS: Irradiated retina at 3 dpf of medaka embryos could be completely regenerated at 18 days after irradiation (21 dpf), although the abnormal layer structures bridging the INL and GCL were transiently formed in the retinas of all the irradiated embryos. Four days after irradiation, embryonic medaka Müller glia were reduced in number but maintained SOX2 expression as in nonirradiated embryos. This finding contrasts with previous reports that 8 dpf medaka larvae could not fully regenerate damaged retinas because of loss of SOX2 expression.

Selective Transarterial Embolization for a Ruptured Persistent Trigeminal Artery Variant Aneurysm.

We report a male patient with a ruptured persistent primitive trigeminal artery variant aneurysm that resulted in a fistula with the cavernous sinus. He presented with left conjunctival hyperemia and exophthalmos. Cerebral angiography revealed a left direct carotid-cavernous fistula; however, a balloon occlusion test determined that the source was actually a ruptured aneurysm located on the trunk of a persistent primitive trigeminal artery. Endovascular trapping of the persistent primitive trigeminal artery was performed, which resulted in fistula occlusion and symptom resolution.

Immunization of rabbits with nematode Ascaris lumbricoides antigens induces antibodies cross-reactive to house dust mite Dermatophagoides farinae antigens.

There are controversial reports on the relationship between helminthic infection and allergic diseases. Although IgE cross-reactivity between nematode Ascaris antigens and house dust-mite allergens in allergic patients have been reported, whether Ascaris or the mite is the primary sensitizer remains unknown. Here we found that immunization of naïve animals with Ascaris lumbricoides (Al) antigens induced production of antibodies cross-reactive to mite antigens from Dermatophagoides farinae (Df). Sera from Bangladeshi children showed IgE reactivity to Ascaris and mite extracts. IgG from rabbits immunized with Al extract exhibited reactivity to Df antigens. Treatment of the anti-Al antibody with Df antigen-coupled beads eliminated the reactivity to Df antigens. In immunoblot analysis, an approximately 100-kDa Df band was the most reactive to anti-Al IgG. The present study is the first step towards the establishment of animal models to study the relationship between Ascaris infection and mite-induced allergic diseases.

Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment.

Pancreatic cancer is notorious for its dismal prognosis. The enhanced permeability and retention (EPR) effect theory posits that nanomedicines (therapeutics in the size range of approximately 10-200 nm) selectively accumulate in tumors. Nanomedicine has thus been suggested to be the "magic bullet"-both effective and safe-to treat pancreatic cancer. However, the densely fibrotic tumor microenvironment of pancreatic cancer impedes nanomedicine delivery. The EPR effect is thus insufficient to achieve a significant therapeutic effect. Intratumoral fibrosis is chiefly driven by aberrantly activated fibroblasts and the extracellular matrix (ECM) components secreted. Fibroblast and ECM abnormalities offer various potential targets for therapeutic intervention. In this review, we detail the diverse strategies being tested to overcome the fibrotic barriers to nanomedicine in pancreatic cancer. Strategies that target the fibrotic tissue/process are discussed first, which are followed by strategies to optimize nanomedicine design. We provide an overview of how a deeper understanding, increasingly at single-cell resolution, of fibroblast biology is revealing the complex role of the fibrotic stroma in pancreatic cancer pathogenesis and consider the therapeutic implications. Finally, we discuss critical gaps in our understanding and how we might better formulate strategies to successfully overcome the fibrotic barriers in pancreatic cancer.

A Case of Horizontal Stent-assisted Coiling for an Aneurysm Arising from Fenestration of the Vertebral Artery: A Technical Case Report.

Horizontal stenting protects the aneurysm neck with stent deployment across the aneurysm neck via the circle of Willis. A saccular aneurysm associated with intracranial arterial fenestration is very rare. Herein, we describe the first case of an unruptured aneurysm related to intracranial arterial fenestration treated with horizontal stenting. A 23-year-old woman presented with a 7-mm broad-necked aneurysm at the fenestration of the right intracranial vertebral artery (VA), which was incidentally found on magnetic resonance imaging. The patient underwent endovascular treatment with horizontal stenting via the vertebrobasilar junction from the contralateral left VA, followed by coil embolization using a jailed microcatheter from the ipsilateral right VA. The procedure was finished with sufficient embolization, and no complications occurred. Horizontal stent delivery via the vertebrobasilar junction for coil embolization of a broad-necked aneurysm arising from the fenestration of the VA is a safe and effective therapeutic strategy.

Allergenicity and cross-reactivity of booklice (Liposcelis bostrichophila): a common household insect pest in Japan.

BACKGROUND: Booklice (Liposcelis bostrichophila) are a common household insect pest distributed worldwide. Particularly in Japan, they infest 'tatami' mats and are the most frequently detected insect among all detectable insects, present at a frequency of about 90% in dust samples. Although it has been hypothesized that they are an important indoor allergen, studies on their allergenicity have been limited. METHODS: To clarify the allergenicity of booklice and the cross-reactivity of this insect allergen with allergens of other insects, patients sensitized to booklice were identified from 185 Japanese adults with allergic asthma using skin tests and IgE-ELISA. IgE-inhibition analysis, immunoblotting and immunoblotting-inhibition analysis were performed using sera from these patients. Allergenic proteins contributing to specific sensitization to booklice were identified by two-dimensional electrophoresis and two-dimensional immunoblotting. RESULTS: The booklouse-specific IgE antibody was detected in sera from 41 patients (22% of studied patients). IgE inhibition analysis revealed that IgE reactivity to the booklouse allergen in the sera from one third of booklouse-sensitized patients was not inhibited by preincubation with extracts from any other environmental insects in this study. Immunoblotting identified a 26-kD protein from booklouse extract as the allergenic protein contributing to specific sensitization to booklice. The amino acid sequence of peptide fragments of this protein showed no homology to those of previously described allergenic proteins, indicating that this protein is a new allergen. CONCLUSIONS: Sensitization to booklice was relatively common and specific sensitization to this insect not related to insect panallergy was indicated in this population.

Analysis of the optimum internal margin for respiratory-gated radiotherapy using end-expiratory phase assessments using a motion phantom.

We aimed to optimize internal margin (IM) determination for respiratory-gated radiotherapy using end-expiratory phase assessments using a motion phantom. Four-dimensional computed tomography (4D CT) data were acquired using a GE LightSpeed RT CT scanner, a respiratory-gating system, and a motion phantom designed to move sinusoidally. To analyze the accuracy of 4D CT temporal resolution, a 25.4 mm diameter sphere was inserted into the motion phantom, and we measured the differences in sphere diameters between static and end-exhalation phase images. In addition, the IM obtained from the maximum intensity projection within the gating window (MIP(GW)) image was compared to theoretical value. Cranial-caudal motion displacement ranged from 5.0 to 30.0 mm, and the respiratory period ranged from 2.0 to 6.0 sec. Differences in sphere diameters between static and end-exhalation phase images ranged from 0.37 to 4.6 mm, with 5.0-mm and 30 mm target displacements, respectively. Differences between the IM obtained from the MIP(GW) and the theoretical values ranged from 1.12 to 6.23 mm with 5.0mm and 30 mm target displacements, respectively. These differences increased in proportion to the target velocity due to a motion artifact generated during tube rotation. In this study, the IMs obtained using the MIPGW image were overestimated in all cases. We therefore propose that the internal target volume (ITV) for respiratory-gated radiotherapy should be determined by adding the calculated value to the end-exhalation phase image. We also demonstrate a methodology for subtracting motion artifacts from the ITV using a motion phantom.

Markers for step-down of inhaled corticosteroid therapy in adult asthmatics.

BACKGROUND: Treatment guidelines recommend the use of inhaled corticosteroids (ICS) as first-line therapy for all stages of persistent asthma. However, it is unknown whether ICS dose reduction in adult asthmatics is compatible with maintaining asthma control. Moreover, there are no predictors of efficacy in maintaining asthma control upon ICS reduction. METHODS: We recruited 90 adult patients with moderate or severe asthma but no clinical symptoms of asthma for at least 6 months. All patients reduced their ICS doses by half but continued taking other asthma-related medications. As a primary outcome, we measured asthma exacerbations during the 12 months following ICS reduction. We also further monitored patients from the above study who had maintained total asthma control for 12 months after ICS reduction and who had continued on their reduced doses of ICS or had further reduced, or stopped, their ICS. RESULTS: Forty of ninety patients (44.4%) experienced exacerbations after ICS reduction (time to first exacerbation: 6.4 ± 3.6 months). Multivariate logistic regression modeling revealed a rank order of predictors of success in ICS reduction while retaining asthma control: acetylcholine (ACh) PC(20) (p < 0.01); length of time with no clinical symptoms before ICS reduction (p < 0.01); FeNO (p = 0.028); and forced expiratory volume in 1 s (FEV(1); % predicted) (p = 0.03). Finally thirty-nine of 50 patients maintained total asthma control for at least 2 years after the initial ICS reduction. CONCLUSIONS: In asthma patients with normalized AChPC(20) of 20mg/mL or 10mg/mL and no clinical symptoms for at least 12 or 24 months it may be possible to successfully reduce ICS without increasing exacerbations for long time.

[Evaluation of Petri dish sampling for assessment of airborne dust mite allergen in Japan].

BACKGROUND: Several allergen sampling methods are available for the assessment of personal or indirect exposure to indoor allergens. As an index of exposure to inhalant allergens, assays of the amount of airborne allergens directly reflect personal exposure. OBJECTIVE: We evaluated the Petri dish sampling method of assessing the level of airborne Dermatophagoides dust mite group 1 (Der 1) allergens. METHODS: We collected settling dust samples from one person's bedroom over a period of 2 years by using a Petri dish, adhesive tape, and a vacuumed reservoir. We also collected settling dust samples from the bedrooms of 42 asthma patients by using a Petri dish and adhesive tape. The amounts of Der 1 collected on the Petri dishes and adhesive tapes were measured by sensitive fluorometric ELISA. RESULTS: Der 1 was detected in all samples by using a Petri dish. The mean coefficient of variation was approximately 15%. We found that Petri dishes set at lower sampling heights contained more Der 1 than those higher up. There were also seasonal changes in the amounts of Der 1 collected, with the highest amounts collected from summer to autumn, and the lowest amounts collected in winter. CONCLUSION: The Petri dish sampling method for collecting settling Der 1 is very simple and can be used as an alternative to personal air sampling, especially in large-scale studies.

Thoracic spinal metastasis as recurrence of borderline Brenner tumor without local recurrence: A case report.

Background: Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2-3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10 %]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26 months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50-60 %]. She received adjuvant radiation of 30 Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11 months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown. Conclusion: We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence.

Thoracic spinal metastasis as recurrence of borderline Brenner tumor without local recurrence: A case report.

Background: Brenner tumor is a rare epithelial ovarian neoplasm that accounts for 2-3% of all ovarian neoplasms. Herein, we report the first case of thoracic spinal metastasis of recurrent Brenner tumor without local recurrence.Case Description.A 70-year-old female presented with a feeling of abdominal distension. Computed tomography revealed cystic lesions in her bilateral ovaries. Blood examination revealed high CA-125 [74.9 U/ml]. We excised bilateral ovaries, uterus, and omentum. Borderline Brenner tumor was diagnosed [Ki-67 labeling index: 10 %]. Follow-up abdominal echo and CA-125 examination revealed no local recurrence. 26 months later she developed paraplegia. Magnetic resonance imaging revealed tumor in the 5th-9th thoracic vertebra and compression of spinal cord at the 6th thoracic vertebra level. Her paraplegia was progressive. We performed semi-urgent partial resection of tumor and release of spinal cord compression. Spinal metastasis from Brenner tumor was diagnosed [Ki-67 labeling index: 50-60 %]. She received adjuvant radiation of 30 Gy in 10 fractions to the 4th-10th thoracic vertebra. After radiation and rehabilitation, she was discharged home on foot. She received adjuvant radiation and chemotherapy but died 11 months after spinal surgery. An autopsy has not been performed on her, and the cause of death is unknown. Conclusion: We report the first case of thoracic metastasis of recurrent Brenner tumor without local recurrence.

Modulation of allergenicity of major house dust mite allergens Der f 1 and Der p 1 by interaction with an endogenous ligand.

Although many allergens bind endogenous molecules other than Abs in the human body, whether the interaction can modulate allergenicity has been unknown. Here, we investigated the effect of the interaction of recombinant major mite group 1 allergens (Der f 1 and Der p 1), which belong to the papain-like cysteine protease family, with an endogenous protease inhibitor, cystatin A, on their allergenicity. Cystatin A bound reduced forms of the allergens, in which the cysteine residue at the catalytic center of the protease activity was reduced by treatment with L-cysteine, but did not bind oxidized forms. Cystatin A partially inhibited the binding of IgE in mite-allergic volunteers' sera to the reduced forms, but unexpectedly enhanced the basophil histamine-releasing activity. A catalytic site-mutant of Der f 1 behaved in terms of histamine release, similarly to the reduced form. Molecular modeling showed that cystatin A interacts with the allergens within a narrow area. The results indicate that interaction with cystatin A reduces the limited number of IgE epitopes of the allergens but enhances their biological activity to release histamine, suggesting a new concept, that interaction between allergens and their endogenous ligands modulates the allergenicity even toward enhancement in the effector phase. On the other hand, i.p. immunization without alum of mice with cystatin A-treated reduced Der f 1 induced less serum Der f 1-specific IgE than immunization with reduced Der f 1 alone, suggesting that endogenous protease inhibitors suppress the induction of allergen-specific IgE, which is dependent on the enzymatic activity of cysteine protease-allergens, in the sensitization process.

Rupture of Anterior Communicating Artery Aneurysm after Intravenous Thrombolysis for Acute Ischemic Stroke: A Case Report.

Objective: Rupture of intracranial aneurysms after tissue plasminogen activator (t-PA) administration for acute ischemic stroke with an unruptured cerebral aneurysm is rare. We report a case of ruptured cerebral aneurysm after t-PA administration. Case Presentation: A 74-year-old woman with dysarthria and left hemiparesis was admitted to our hospital, and acute lacunar infarction was found in the right corona radiata. One hour after t-PA administration, she complained of sudden headache and nausea, and her consciousness level deteriorated. Subarachnoid hemorrhage due to rupture of the anterior communicating aneurysm was confirmed and coil embolization was performed. Conclusion: T-PA administration for acute ischemic stroke with an unruptured cerebral aneurysm risks rupture of the cerebral aneurysm, and careful judgment is needed in each case.

Carotid Cavernous Fistula during Thrombectomy for Acute Ischemic Stroke: A Case Report.

Objective: We report a rare complication, carotid cavernous fistula (CCF), due to vessel perforation during thrombectomy for acute ischemic stroke (AIS). Case Presentation: An 88-year-old woman underwent thrombectomy for left C4 occlusion of the internal carotid artery. There was strong resistance at the medial C4 while the microguidewire was guided distally, and a CCF was found after deploying and retrieving the stent. It was thought to have been caused by perforation due to intracranial atherosclerotic stenosis of the internal carotid artery. Conclusion: During thrombectomy for intracranial large vessel occlusion underlying intracranial atherosclerotic stenosis, the risk of vascular injury should be kept in mind.

Tubulointerstitial nephritis and uveitis syndrome following meningitis and systemic lymphadenopathy with persistent Toxoplasma immunoglobulin M: a case report.

BACKGROUND: Tubulointerstitial nephritis and uveitis syndrome is a rare lymphocyte-related oculorenal inflammatory disease presumed to be associated with drug use and infectious agents. Toxoplasma gondii is one of such pathogens that could exhibit encephalitis, meningitis, and uveitis in immunocompromised or in some immunocompetent individuals. If the immunoglobulin M of Toxoplasma is positive on screening, the interpretation of the result is not simple, especially when immunoglobulin M stays positive persistently. CASE PRESENTATION: A 34-year-old Asian male developed fever, headache, and lymphadenopathy with tenderness, which was initially diagnosed as meningitis. Antibiotics were started, and diclofenac sodium was used for the fever. Although his symptoms were alleviated in a week by the treatment, gradual decline in renal function was noted, prompting a renal biopsy that indicated acute granulomatous interstitial nephritis. A week later, tenderness in both eyes with blurred vision appeared and revealed iritis and keratic precipitations in both eyes; hence, the diagnosis of acute tubulointerstitial nephritis and bilateral uveitis syndrome was made. Toxoplasma gondii-specific immunoglobulin G and immunoglobulin M titers were both positive. Although we could not rule out recent infection of Toxoplasma gondii, which may cause uveitis initially, Toxoplasma immunoglobulin G avidity test indicated a distant infection, which allowed us to rule out meningitis and uveitis as responsible for the complication of recent Toxoplasma gondii infection. Drug-induced lymphocyte stimulation test, or lymphocyte transformation test of diclofenac sodium, was solely positive among the tested drugs. Uveitis was alleviated only with ophthalmic steroid, and renal function returned to normal without administration of systemic steroid. CONCLUSIONS: We experienced a case of diclofenac-induced tubulointerstitial nephritis and uveitis syndrome. In ruling out infections, Toxoplasma immunoglobulin M was persistently positive, and Toxoplasma immunoglobulin G avidity test indicated a "distant" infection. From these two results, we ruled out recent infection. However, it should be noted that "distant" infection indicated by commercial immunoglobulin G avidity is still a multiplex profile consisting of reinfection, reactivation, and latent infection. Narrowing down the infection profile of Toxoplasma is challenging in some cases. Therefore, careful diagnosis and extended follow-up of such patients are needed.