Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity

Introduction

B-cell depletion has become a common treatment strategy in anti-TNF-refractory rheumatoid arthritis (RA). Although the exact mechanism of how B-cell depletion leads to clinical amelioration in RA remains to be elucidated, repetitive treatment with B-cell-depleting agents leading to long-term B-cell depletion has been reported to be beneficial. The latter has led to the hypothesis that the beneficial effects of B-cell depletion might act through their influence on pathogenic autoreactive plasma cells.

Methods

In this study, we investigated the effects of a fixed retreatment regimen with anti-CD20 mAbs on the humoral (auto)immune system in a cohort of therapy-refractory RA patients.

Results

Fixed retreatment led to long-term B-cell depletion in peripheral blood, bone marrow and, to a lesser extent, synovium. Also, pathologic autoantibody secretion (that is, anticitrullinated peptide antibodies (ACPAs)) was more profoundly affected by long-term depletion than by physiological protective antibody secretion (that is, against measles, mumps and rubella). This was further illustrated by a significantly shorter estimated life span of ACPA-IgG secretion compared to total IgG secretion as well as protective antibody secretion.

Conclusion

By studying plasma cell function during an extensive 2-year period of B-cell depletion, autoantibody secretion was significantly shorter-lived than physiologically protective antibody secretion. This suggests that the longevity of autoreactive plasma cells is different from protective long-lived plasma cells and might indicate a therapeutic window for therapies that target plasma cells.     

Distribution and abundance of the intertidal saltmarsh beetle, Bledius spectabilis

ABSTRACT.

• 1 The burrowing intertidal beetle Bledius spectabilis Kraatz (Coleoptera: Staphylinidae) occurs on all but the very youngest marshes on Scolt Head Island, Norfolk, U.K., and may reach densities of up to 4000 m^?2 (combined adult and larval densities).
• 2 The beetles are restricted to a narrow band about 1m wide along the edges of creeks draining the low marsh areas of the island, and the vertical range is restricted to a zone between 0.8 and 1.55m above Ordnance Datum. The majority of the aggregations and the highest densities are between 1.2 and 1.3m O.D., that is between about 24 and 40cm below MHWN (mean high water at neap tides).
• 3 Poor drainage, in particular the presence of long-standing pools of water over the soil surface, is important in restricting the beetles to well-drained edge regions.
• 4 Transplant experiments suggest that displacement by saltmarsh vegetation, in particular Halimione portulacoides (L.) Aell., sets the upper limit of the beetles’distribution.
• 5 The zonation of B.spectablis fits well into the general scheme that has been proposed for the zonation of marine animals from rocky shores.
• 6 The beetles produce large (3–6 mm diameter), rapidly draining, abundant (up to 9% of soil volume) and persistent burrows. We suggest that these beetle aggregations may play an important role in the development of the saltmarsh.

     

Thyroid disease is a favorable prognostic factor in achieving sustained virologic response in chronic hepatitis C undergoing combination therapy: A nested case control study

Background

Interferon-α in combination with ribavirin is the current gold standard for treatment of chronic hepatitis C. It is unknown if the development of autoimmune thyroid disease (TD) during treatment confers an improved chance of achieving sustained virologic response. The aim of this study is to assess the chance of achieving sustained virologic response (SVR) in patients who developed TD during treatment when compared with those who did not.

Methods

We performed a tertiary hospital-based retrospective nested case-control analysis of 19 patients treated for hepatitis C who developed thyroid disease, and 76 controls (matched for age, weight, gender, cirrhosis and aminotransferase levels) who did not develop TD during treatment. Multivariate logistic-regression models were used to compare cases and controls.

Results

The development of TD was associated with a high likelihood of achieving SVR (odds ratio, 6.0; 95% confidence interval, 1.5 to 24.6) for the pooled group containing all genotypes. The likelihood of achieving SVR was increased in individuals with genotype 1 HCV infection who developed TD (odds ratio, 5.2; 95% confidence interval, 1.2 to 22.3), and all genotype 3 patients who developed TD achieved SVR.

Conclusions

Development of TD during treatment for hepatitis C infection is associated with a significantly increased chance of achieving SVR. The pathophysiogical mechanisms for this observation remain to be determined.

Trial Registration

The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRB12610000830099     

The life history and population biology of an intertidal aphid,Pemphigus trehernei Foster

• 1 The fluctuations in the density and composition of populations of Pemphigus trehernei, an aphid that lives on the roots of the halophyte Aster tripolium, were followed on an area of saltmarsh on the north Norfolk coast between 1971 and 1973.
• 2 The aphid has a typical Pemphigus life-cycle, but the emphasis is on the non-sexual anholocycle. Many diapausing aphids overwinter on the marsh and relatively few alates fly to or from it.
• 3 The aphids are confined to the top 11 cm of soil and are highly aggregated: the dispersion of the population can be fitted to the negative binomial. The absolute density of the populations is relatively low, with a mean value of about 2000 aphids/m² of available marsh area.
• 4 Temperature, host-plant growth and fungal attack are probably the most important factors affecting seasonal population fluctuations. Up to 50% of the populations may be infected with the fungus Metarrhizium anisopliae, which is widespread in the soil.

     

Classification of water beetle assemblages in arable fenland and ranking of sites in relation to conservation value

SUMMARY. 1. Water beetles were recorded from 157 sites around the Wash, England, in 1986. Most sites were ditches in arable land. Eight main types of water beetle assemblage were identified by multivariate analysis. The habitats of these assemblages were characterized by measurement of a range of physical and chemical factors.
2. Of the 130 species recorded, four are listed in the British Red Data Book and a further thirty-five are rated as Nationally Notable. Records from 1904 to 1938 for the same area indicate that only three species have been lost in the subsequent period of intensification of water management and arable farming. A rich water beetle fauna can thus survive in drainage systems in arable fen.
3. Vegetation management was important in maintaining the 'species quality score', proposed as a measure of conservation value, of larger ditches but management reduced the species quality of one type of assemblage associated with smaller ditches. One type of assemblage was found only in ditches subject to management.