Immune therapy of lupus: what is on the horizon?

Systemic lupus erythematosus (SLE) is a complex disease whichhas posed a continuing challenge to scientists and cliniciansof diverse areas of specialization. It serves as a model forthe study of the mechanisms of autoimmunity—providingan important basis for the development of novel targeted therapiesin lupus and related conditions. The pathophysiology of SLE stems from the abnormal clearanceof apoptotic cells and/or endothelial activation. Material fromdying cells such as apoptotic blebs that are not efficientlyremoved may act as antigenic stimuli and lead to the developmentof autoantibodies with consequent formation of immune complexesand an inflammatory response in a variety of organ systems [1].This     

The Effect of Total Blood Exchange with PHP Solution on Cardiac Xenotransplantation

Abstract: Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridox-alated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15–20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 ± 74 min and to 10.4 ± 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.     

High-dose intravenous immunoglobulin therapy improved muscle strength in a patient with multifocal motor neuropathy and antibodies against the glycolipid LK1

We report improvement in muscle strength in a patient with multifocal motor neuropathy (MMN) when given high-dose intravenous immunoglobin (i.v.-Ig) treatment. The patient had asymmetrical limb weakness, atrophy and absent or weak reflexes, but no sensory disturbances. Neurography showed multiple conduction blocks in peripheral motor nerves but no sensory nerve abnormalities. Serum and anti-GM1 antibodies were not found, however, the patient had serum antibodies against the glycolipid LK1, an epitope found both in glycolipid and also in some glycoproteins in peripheral nerve myelin. Muscle strength improved 5 days after i.v.-Ig therapy, and lasted about 10 weeks. Repeated courses of treatment resulted in similar improvement. This is, to our knowledge, the first patient reported with MMN found to have antibodies against the glycolipid LK1.     

抗淋球菌IgA蛋白酶单克隆抗体特性的初步研究

本文对以重组淋球菌ＩｇＡ蛋白酶为抗原制备的７株特异性ＭｃＡｂ的特性进行了初步研究。结果有５株（１Ｃ８、１Ｅ５、１Ｆ１１、１Ｇ３和２Ｅ６）能中和淋球菌ＩｇＡ蛋白酶活性。经相加试验初步证明，其中１Ｆ１１、２Ｇ３与其它３株ＭｃＡｂ的作用位点不同。因此，淋球菌ＩｇＡ蛋白酶至少存在３个中和表位。     

Immunohistochemical differentiation of metastases of renal carcinomas versus other carcinomas with anti-γGT monoclonal antibody 138H11

Aims : Adenocarcinomas account for about 60% of metastatic cancers of unknown primary (CUP) site. In such a clinical CUP situation, histopathologists are challenged to differentiate renal cell carcinomas (RCC) from other adenocarcinomas with similar immunophenotypes, especially chemotherapeutically treatable mammary and ovarian carcinomas. Methods and results : Recently, we produced a monoclonal antibody (mAb), designated 138H11, against human gamma-glutamyltransferase (γGT), which stained over 98% primary clear cell and chromophilic RCC on frozen sections. The 138H11 epitope could not be stained using conventional techniques in most paraffin-embedded sections of the same origin, due to destruction by formalin fixation below the detection level. Here, we demonstrate that mAb 138H11 can specifically stain γGT in paraffin-embedded primary and metastatic RCC after enhancement with an ultrasensitive immunohistochemical method. We analysed a selected subgroup of adenocarcinomas with immunophenotypes which would not allow a differentiation from RCC in a CUP situation. We found a predominantly membranous expression of the 138H11 target antigen in 26/51 primary RCC and 15/34 metastatic RCC. In contrast, all 43/43 primary ovarian and bronchial carcinomas as well as 54/54 metastases of ovarian, mammary, bronchial and gastric carcinomas were negative for mAb 138H11. Conclusions : The data suggest that mAb 138H11 is useful for the immunohistochemical differentiation of RCC from other metastatic adenocarcinomas if the primary site of the tumour is not known.     

Effect of Glass Transition Temperature on the Stability of Lyophilized Formulations Containing a Chimeric Therapeutic Monoclonal Antibody

Purpose. The purpose of this study is to highlight the importance of knowing the glass transition temperature, T_g, of a lyophilized amorphous solid composed primarily of a sugar and a protein in the interpretation of accelerated stability data. Methods. Glass transition temperatures were measured using DSC and dielectric relaxation spectroscopy. Aggregation of protein in the solid state was monitored using size-exclusion chromatography. Results. Sucrose formulation (T_g ~ 59°C) when stored at 60°C was found to undergo significant aggregation, while the trehalose formulation (T_g ~ 80°C) was stable at 60°C. The instability observed with sucrose formulation at 60°C can be attributed to its T_g (~59°C) being close to the testing temperature. Increase in the protein/sugar ratio was found to increase the T_gs of the formulations containing sucrose or trehalose, but to different degrees. Conclusions. Since the formulations exist in glassy state during their shelf-life, accelerated stability data generated in the glassy state (40°C) is perhaps a better predictor of the relative stability of formulations than the data generated at a higher temperature (60°C) where one formulation is in the glassy state while the other is near or above its T_g.     

Effects of specific antibodies on the ultrastructure of mouse oocytes

The effects of antiovarian antiserum and monoclonal antibodies to the oolemma antigens on the ultrastructure of mouse oocytes and their microenvironment are studied. The antioolemma monoclonal antibodies cause more pronounced degenerative changes in the oocyte that in its microenvironment. Antiovarian antiserum induces greater changes in the microenvironment than in the oocyte. Changes induced in the oocyte by the antiserum are secondary relative to changes occurring in the microenvironment, while changes observed in the oocyte treated with monoclonal antibodies are primary. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 1, pp. 115–119, January, 1997     

IgA antiendomysium antibodies in human umbilical cord sections as a screening test in relatives of patients with celiac disease

We performed the serum IgA antiendomysium antibody (EmA) assay by indirect immunofluorescence on human umbilical cord sections in 86 subjects with celiac disease, in 187 first-degree relatives of such patients, and in a control group of 68 unrelated subjects, to investigate the suitability of the method in the screening of populations at risk of gluten sensitivity. Conventional EmA assay using monkey esophagus sections was performed in parallel experiments. The results obtained showed a perfpect correlation between the two methods. All the celiac patients and none of the controls were positive for EmA. EmA positivity was also observed in 11 apparently healthy relatives: intestinal biopsy performed in five of them invariably showed villous atrophy and increase of mucosal lymphocytes. Taking into account the low cost of EmA assay on human umbilical cord, especially when compared to monkey esophagus sections, the method is probably suitable and effective in identifying latent, asymptomatic gluten sensitivity in at-risk populations.     

Familial Sneddon's syndrome

We report the familial occurrence and apparent autosomal dominant inheritance of Sneddon's syndrome with variable clinical expression. The proband, a 40-year-old woman, presented with livedo reticularis and progressive neurological deterioration following a stroke. The diagnosis was confirmed by cerebral angiogram and skin biopsy, both showing the characteristic findings. Two of the patient's sisters were reported to have been similarly affected in the past. Her mother, two additional siblings and five of her seven children exhibited various vasospastic skin phenomena. Familial aggregation of this disorder may be common and a genetic basis may be involved in its pathogenesis.     

Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan. © 1993 Wiley-Liss, Inc.