Central diabetes insipidus with anti-rabphilin-3A antibody positivity causing hypovolemic shock after resection of tumorous lesions in the pelvic cavity.

A 36-year-old female was pointed out to have liver enzyme elevation by routine health checkup. Subsequent contrast-enhanced CT scan identified gigantic uterine fibroids and retroperitoneal tumor. She was referred to the gynecologist at JA Toride Medical Center and planned to undergo a uterus enucleation and biopsy of the retroperitoneal tumor. The surgery was conducted without any troubles. After the surgery, the patient presented polyuria with urine volume 10-20 L a day and developed hypovolemic shock. Laboratory test revealed hypotonic urine and hypernatremia. Arginine vasopressin (AVP) loading test suggested shortage of endogenous vasopressin. Since the subcutaneous administration of AVP was not sufficient to control the urine volume, continuous intravenous infusion of AVP was initiated. After achieving hemodynamic stability, the treatment was switched to oral desmopressin. MRI finding indicated attenuation of high signal in posterior pituitary in T1 weighted image while neither enlargement of pituitary nor thickening of pituitary stalk was indicated by enhanced MRI. Hypertonic salt solution test indicated no responsive elevation of AVP, confirming the diagnosis of central diabetes insipidus (CDI). Her anterior pituitary function was preserved. Only anti-rabphilin-3A antibody was found positive in the serum of the patient, while other secondary causes for CDI were denied serologically and radiologically. Hence, lymphocytic infundibuloneurohypophysitis　(LINH) was suspected as the final diagnosis. Hormonal replacement therapy by nasal desmopressin was continued and the patient managed to control her urine volume. In cases of CDI considered idiopathic with conventional examinations, anti-rabphilin-3A antibody may be a clue for determining the cause as LINH.

Transition of lymphocyte subsets in peritoneal dialysis effluent and its relationship to peritoneal damage.

Objective: Peritoneal function during peritoneal dialysis (PD) declines over time due to peritoneal inflammation; however, the immunological mechanism has not been fully clarified. Here, we examined changes in each cellular fraction in the peritoneal dialysis effluent by flow cytometry and their relationship to peritoneal damage. Patients and Methods: We enrolled 23 patients who began PD between 2006 and 2017 and had available datasets of the peritoneal equilibration test and flow cytometric analysis for at least three consecutive visits, with an interval of six months from six months after introducing PD. The levels and changes in each cellular fraction, dialysate/plasma (D/P) creatinine ratio, and the forward scatter (FSC) ratio of mesothelial cells to lymphocytes were compared using a simple linear regression analysis. Results: Among the examined variables, only the fraction of CD8+ TCM cells during the first observation was significantly correlated with the change rate in the D/P creatinine ratio (ß=1.47, P=0.001, adjusted R2=0.379). The CD8+ naïve T and CD8+ TCM cell fractions were negatively correlated with the change rate of the D/P creatinine ratio (naïve T cells: ß=-0.058, P=0.022, adjusted R2=0.188; TCM cells: ß=-0.096, P=0.046, adjusted R2=0.137). In addition, the change rates of the D/P creatinine ratio tended to be higher, though not significantly (one way ANOVA; P=0.080), in accordance with the increase in the change rate of the CD8+ effector memory T cells (TEM). Conclusion: The CD8+ naïve T and TCM cells may transition into TEM cells by repeated exposure to the dialysate over time. The TEM cells residing in the peritoneum may play a significant role in the progression of peritoneal damage.

Predominant tubulointerstitial lupus nephritis with preceding pernicious anemia.

Predominant tubulointerstitial nephritis with negligible glomerular lesions is a rare form of lupus nephritis. Although tubulointerstitial changes occur in two-thirds of patients with lupus nephritis, these lesions were mostly accompanied by glomerulonephritis. Predominant tubulointerstitial lupus nephritis has been reported to be only 13 cases in the literature as far as we surveyed. Here, we present a case of a 72-year-old male who had pancytopenia associated with pernicious anemia and later developed a mild proteinuria and renal insufficiency. Although urinary tubulointerstitial markers increased, serological screening tests for tubulointerstitial nephritis were all negative. Three months later, the patient was diagnosed as systemic lupus erythematosus, based on polyarthritis, positive antinuclear antibody, immunological disorder and hematological disorder. Renal biopsy revealed severe infiltration of mononuclear cells in the interstitium with minimal abnormalities in glomeruli. Positive IgG and C1q staining with immunofluorescence antibody method in the tubular basement membrane and dense deposits in the same region with electron microscopy confirmed a diagnosis of predominant tubulointerstitial lupus nephritis. Since the patient's renal function declined rapidly, treatment with intravenous 500 mg methyl prednisolone followed by 40 mg/day of oral prednisolone was initiated. The patient's renal function improved and became stable even after tapering of prednisolone. Although lupus nephritis is generally accompanied by multiple symptoms such as fever, malaise, arthralgia, rashes, this case showed only pernicious anemia and tubulointerstitial nephritis initially.

Gap junction intercellular communications regulate NK cell activation and modulate NK cytotoxic capacity.

Gap junctions (GJs) mediate intercellular communication between adjacent cells. Previously, we showed that connexin 43 (Cx43), the main GJ protein in the immune system, mediates Ag transfer between human dendritic cells (DCs) and is recruited to the immunological synapse during T cell priming. This crosstalk contributed to T cell activation, intracellular Ca(2+) responses, and cytokine release. However, the role of GJs in NK cell activation by DCs and NK cell-mediated cytotoxicity against tumor cells remains unknown. In this study, we found polarization of Cx43 at the NK/DC and NK/tumor cell-contact sites, accompanied by the formation of functional GJs between NK/DCs and NK/tumor cells, respectively. Cx43-GJ-mediated intercellular communication (GJIC) between human NK and DCs was bidirectional. Blockage of Cx43-GJIC inhibited NK cell activation, though it affected neither the phenotype nor the function of DCs. Cx43 knockdown or inhibition using mimetic peptides greatly reduced CD69 and CD25 expression and IFN-γ release by DC-stimulated NK cells. Moreover, blocking Cx43 strongly inhibited the NK cell-mediated tumor cell lysis associated with inhibition of granzyme B activity and Ca(2+) influx. Our data identify a novel and active role for Cx43-GJIC in human NK cell activation and antitumor effector functions that may be important for the design of new immune therapeutic strategies.