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During the 12th International Workshop on Autoantibodies and Autoimmunity held in Sao Paulo, Brazil, on August 28, 2014, a full day session was devoted to establishing a consensus on the nomenclature of staining patterns observed in the antinuclear antibody (ANA) indirect immunofluorescence test on HEp-2 cells. The current report summarizes the collective agreements with input from the host Brazilian and international communities that represented research, clinical, and diagnostic service laboratories. Patterns are categorized in three major groups (nuclear, cytoplasmic, and mitotic patterns) and each pattern has been defined and described in detail. The consensus nomenclature and representative patterns are made available online at the international consensus on antinuclear antibody pattern (ICAP) website (). To facilitate continuous improvement and input, specific comments on ICAP are encouraged and these will be discussed in subsequent ICAP meetings. The ultimate goal with the establishment of the ICAP is to promote harmonization and understanding of autoantibody test nomenclature, as well as interpretation guidelines for ANA testing, thereby optimizing usage in patient care.

The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells. The International Consensus on ANA Patterns (ICAP) initiative has previously reached consensus on the nomenclature and definitions of HEp-2 IIFA patterns. In the current paper, the ICAP consensus is presented on the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria.

Lipoarabinomannans are major mycobacterial antigens capable of modulating the host immune response; however, the molecular basis underlying the diversity of their immunological properties remain an open question. In this study a new extraction and purification approach was successfully applied to isolate ManLAMs (lipoarabinomannans with mannosyl extensions) from bacillus Calmette Gué rin leading to the obtention of two types of ManLAMs namely parietal and cellular. Structurally, they were found to differ by the percentage of mannooligosaccharide caps, 76 and 48%, respectively, and also, thanks to a new analytical method, by the structure of the phosphatidyl-myo-inositol anchor lipid moiety. A novel fatty acid in the mycobacterium genus assigned to a 12-O-(methoxypropanoyl)-12-hydroxystearic acid was the only fatty acid esterifying C-1 of the glycerol residue of the parietal ManLAMs, while the phosphatidyl unit of the cellular ManLAMs showed a large heterogeneity due to a combination of palmitic and tuberculostearic acid. Finally, parietal and cellular ManLAMs were found to differentially affect interleukin-8 and tumor necrosis factor-␣ secretion from human dendritic cells. We show that parietal but not cellular ManLAMs were able to stimulate tumor necrosis factor-␣ secretion from dendritic cells. From these studies we propose that the 1-[12-O-(methoxypropanoyl)-12-hydroxystearoyl]-sn-glycerol part is the major cytokineregulating component of the ManLAMs. It seems likely that modification of the ManLAM lipid part, which may occur in hostile environments, could regulate macrophagic mycobacterial survival by altering cytokine stimulation.Tuberculosis remains the leading cause of human death among the infectious diseases with over 3 million deaths each year (1). The decline in tuberculosis in the developed countries has been reversed by the tuberculosis cases arising in AIDS patients, among the homeless, and by the emergence of Mycobacterium tuberculosis strains resistant to the first-line drugs, which are isoniazid and ethambutol. Also, from different trials, the efficiency of BCG 1 vaccine to prevent tuberculosis was found to range from 0 to 80% (2, 3).Virulent mycobacteria survive and multiply within phagosomes of mononuclear phagocytes. Despite conflicting results, there is a consensus that phagosomes containing M. tuberculosis do not fuse with lysosomes and resist acidification (4). This survival can also be correlated with the macrophage bactericide activity, which appears to be modulated by mycobacterial cell wall components (5, 6).From a molecular point of view, cell wall lipoarabinomannans (LAMs) are clearly demonstrated to be pivotal mycobacterial antigens. They regulate TNF-␣ production by phagocyte (5) and block the transcriptional activation of INF-␥ (6), thereby influencing the intramacrophagic survival of mycobacteria. For instance, LAMs (PI-GAMs) from Mycobacterium smegmatis, a fast growing mycobacterium that does not survive inside the macrophages, were found to stimulate phagocyte TNF-␣ production ...

Objective. A prospective study was performed to assess the usefulness of contrast-enhanced color Doppler ultrasound (CDUS) in the evaluation of intraarticular vascularization of finger joints in patients with rheumatoid arthritis (RA).Methods. We investigated 198 finger joints in 46 patients with RA, and 80 finger joints in 10 healthy volunteers. Joints with varying levels of clinical activity of inflammation were classified as being active, moderately active, or inactive. CDUS was performed with a high-frequency multi-D linear array transducer. A microbubble-based ultrasound (US) contrast agent (Levovist; Schering, Berlin, Germany) was intravenously infused. Doppler findings were rated on the basis of both unenhanced and contrast-enhanced CDUS images.Results. Healthy joints showed no intraarticular vascularization on either unenhanced or contrastenhanced CDUS. Unenhanced CDUS detected intraarticular vascularization in 7 (8%) of 83 inactive joints, in 31 (52%) of 60 moderately active joints, and in 32 (58%) of 55 active joints. Contrast-enhanced CDUS detected intraarticular vascularization in 41 (49%) of 83 joints with inactive RA, in 59 (98%) of 60 joints with moderately active RA, and in all 55 joints with active RA. Detection of intraarticular vascularization was improved by administration of the microbubble-based US contrast agent (P < 0.001). Contrast-enhanced CDUS demonstrated differences in intraarticular vascularization between joints with inactive RA and those with active RA (P < 0.001), between joints with inactive RA and those with moderately active RA (P < 0.001), and between joints with moderately active RA and those with active RA (P < 0.001). Conclusion. The use of a microbubble-based US contrast agent significantly improved the detection of intraarticular vascularization in the finger joints of patients with RA. This technique seems to be a useful adjunct in the assessment of disease activity.A crucial event in the pathogenesis of rheumatoid arthritis (RA) is the development of pannus (1). Proliferation of pannus is an early event in the course of the disease and can be seen before destruction of cartilage and bone. Vascularization of pannus appears to be crucial to its invasive and destructive behavior (2,3). Radiography is currently the method used for assessing the degree of actual joint destruction (4). Contrastenhanced magnetic resonance imaging (MRI) has also been utilized for this purpose, but this technique is not yet routinely available and is relatively cost-intensive and time-consuming (5,6).Hypervascularization of the pannus is usually caused by inflammatory activity. Color Doppler ultrasound (CDUS) imaging allows for detection of vascularity (6-11). CDUS combines the imaging capabilities of conventional B-mode ultrasound (US) with the bloodflow determinations of Doppler US and permits assessment of both the anatomy and the characteristics of blood flow of the vessels at specific sites. However, this technique is limited in the detection of slow flow and flow in small vessels. The add...

Because of the heterogeneity in tumor biology with respect to antibody uptake and clearance, we suggest that either intrapatient dose escalation approaches or larger, more precisely defined patient cohorts would be preferable to conventional strategies in the design of phase I studies with antiangiogenic compounds like HuMV833.

The International Consensus on ANA Patterns (ICAP) was initiated as a workshop aiming to thoroughly discuss and achieve consensus regarding the morphological patterns observed in the indirect immunofluorescence assay on HEp-2 cells. One of the topics discussed at the second ICAP workshop, and addressed in this paper, was the harmonization of reporting ANA test results. This discussion centered on the issue if cytoplasmic and mitotic patterns should be reported as positive or negative. This report outlines the issues that impact on two major different reporting methods. Although it was appreciated by all participants that cytoplasmic and mitotic patterns are clinically relevant, implications for existing diagnostic/classification criteria for ANA-associated diseases in particular hampered a final consensus on this topic. Evidently, a more concerted action of all relevant stakeholders is required. Future ICAP workshops may help to facilitate this action.