Autoantibodies' titre modulation by anti-BlyS treatment in systemic lupus erythematosus.

OBJECTIVE: The objective of this study was to analyse autoantibodies' titres modulation during belimumab treatment in 50 patients with systemic lupus erythematosus (SLE). METHODS: Sera were collected at belimumab start (T0) and every six months until the 24th month. Disease activity index (SLEDAI-2K) was analysed at every timepoint. High avidity anti-dsDNA was detected by radioimmunological method, anti-ENA, anti-cardiolipin antibodies (aCL), anti-ß2 glycoprotein I (anti-ß2GPI) were analysed by ELISA. RESULTS: Fifty patients with SLE (mean SLEDAI-2K: 7.18 ± :3), mean age of 39 ± 11 years and mean follow-up of 13 ± 7.8 years were enrolled. A significant decrease of anti-dsDNA and anti-ß2GPI IgM titres was observed at all timepoints. IgG aCL titre showed significant decrease only at T18. Anti-dsDNA negativization was detected in 21%, anti-ß2GPI IgG in 33% and aCL IgG in 30% of sera, mostly at T6. Anti-ribosomal showed a significant titre decrease at T6 and T12, with negative seroconversion at T18. Anti-Sm titre significantly dropped down at T6, then remained stable during the time. Significant correlations were found between anti-dsDNA and anti-ribosomal titre and between SLEDAI ratio (SLEDAI value/SLEDAI T0) and anti-ribosomal titre ratio (value/value T0). CONCLUSIONS: Belimumab treatment induced a significant reduction of SLE-specific autoantibodies titre and IgM anti-ß2GPI. Anti-ribosomal titre decrease correlates with anti-dsDNA titre and disease activity improvement.

Antinuclear antibodies in Frontotemporal Dementia: the tip's of autoimmunity iceberg?

Recent studies suggest a role of the autoimmune system dysregulation in Frontotemporal dementia (FTD). In the present study, we performed a broad immunological screening in a large sample of sporadic FTD patients. We reported a significant increase of antinuclear autoantibodies (ANA) positivity in 100 FTD patients as compared to 100 healthy controls (HC) (60% vs. 13%, p < .001). In FTD, ANA-positive and ANA-negative patients did not differ for any clinical feature. These data extend and further confirm autoimmune dysregulation in FTD. However, it still remains to be clarified whether these antibodies have a potential pathogenic role or represent simply an epiphenomenon.

Are the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and the undifferentiated connective tissue disease (UCTD) related to each other? A case-control study of environmental exposures.

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is an entity that includes different autoimmune conditions observed after exposure to an adjuvant. Patients with undifferentiated connective tissue disease (UCTD) present many signs and symptoms of ASIA, alluding to the idea that an exposure to adjuvants can be a trigger also for UCTD. The aim of this case-control study was to investigate exposure to adjuvants prior to disease onset in patients affected by UCTD. Ninety-two UCTD patients and 92 age- and sex-matched controls with no malignancy, chronic infections, autoimmune disease nor family history of autoimmune diseases were investigated for exposure to adjuvants. An ad hoc-created questionnaire exploring the exposure to vaccinations, foreign materials and environmental and occupational exposures was administered to both cases and controls. Autoantibodies were also analyzed (anti-nuclear, anti-extractable nuclear antigens, anti-double-stranded DNA, anti-cardiolipin, anti-ß2 glycoprotein I). UCTD patients displayed a greater exposure to HBV (p = 0.018) and tetanus toxoid (p < 0.001) vaccinations, metal implants (p < 0.001), cigarette smoking (p = 0.006) and pollution due to metallurgic factories and foundries (p = 0.048) as compared to controls. UCTD patients exposed to major ASIA triggers (vaccinations, silicone implants) (n = 49) presented more frequently with chronic fatigue (p < 0.001), general weakness (p = 0.011), irritable bowel syndrome (p = 0.033) and a family history for autoimmunity (p = 0.018) in comparison to non-exposed UCTDs. ASIA and UCTD can be considered as related entities in the "mosaic of autoimmunity": the genetic predisposition and the environmental exposure to adjuvants elicit a common clinical phenotype characterized by signs and symptoms of systemic autoimmunity.

Inversion and eversion strengths in the weightbearing ankle of young women. Effects of plantar flexion and basketball shoe height.

Maximum isometric ankle inversion and eversion muscle strengths were measured under full unipedal weightbearing in 20 healthy young adult women. When the women wore a low-top shoe, the mean (standard deviation) maximum external eversion moments resisted with the foot in 0 degrees and 32 degrees of ankle plantar flexion were 24.1 (7.6) and 24.1 (8.1) N x m, respectively, while the corresponding values for maximum inversion moments resisted were 14.7 (6.8) and 17.4 (6.4) N x m, respectively. Both shoe height and ankle plantar flexion affected the overall inversion moment resisted by 17% (P = 0.03) at 0 degrees of ankle plantar flexion to 11.9% (P = 0.003) at 32 degrees of ankle plantar flexion. However, neither shoe height nor ankle plantar flexion significantly affected the maximum eversion moment resisted. Although eversion muscle strength of the young women averaged 39% less than the corresponding value found in young men, the sex difference was not significant when ankle strengths were normalized by body size (body weight x height). Thus, when data from healthy young men and women were averaged, eversion and inversion strengths averaged 1.6% and 2.7%, respectively, of body weight x height.

Basketball shoe height and the maximal muscular resistance to applied ankle inversion and eversion moments.

To determine if the height of a basketball shoe alters the maximal inversion and eversion moment that can be actively resisted by the ankle in the frontal plane, we tested 20 healthy, young adult men with no recent ankle injuries. Subjects underwent unipedal functional ankle strength testing under weightbearing conditions at 0 degrees, 16 degrees, and 32 degrees of ankle plantar flexion using a specially designed testing apparatus. Testing was performed with the subject wearing either a low- or a three quarter-top basketball shoe. Shoe height did not significantly affect an individual's ability to actively resist an eversion moment at any angle of ankle plantar flexion. However, tests at 0 degrees of ankle plantar flexion demonstrated that the three quarter-top basketball shoe we tested significantly increased the maximal resistance to an inversion moment by 29.4%. At 16 degrees of ankle plantar flexion, inversion resistance was also significantly improved by 20.4%. These results show that athletic shoe height can significantly increase the active resistance to an inversion moment in moderate ankle plantar flexion. The findings apply to a neutral foot position in the frontal plane, an orientation equivalent to the early phase of a potential ankle sprain.

What best protects the inverted weightbearing ankle against further inversion? Evertor muscle strength compares favorably with shoe height, athletic tape, and three orthoses.

We measured the maximal isometric eversion moment developed under full weightbearing in 20 healthy adult men (age, 24.4 +/- 3.4 years; mean +/- SD) with their ankles in 15 degrees of inversion. Tests were performed at both 0 degree and 32 degrees of ankle plantar flexion in low- and in three-quarter-top shoes with and without adhesive athletic tape or one of three proprietary ankle orthoses. At 0 degree of ankle plantar flexion, the mean maximal voluntary resistance of the unprotected ankle to an inversion moment was 50 +/- 8 N-m; this increased by an average of 12% (or 6 N-m) when the subject wore a three-quarter-top basketball shoe. The maximal voluntary resistances to inversion moments developed with the ankles further protected by athletic tape or any of three orthoses were not significantly different. Biomechanical calculations suggest that at 15 degrees of inversion the fully active ankle evertor muscles isometrically developed a moment up to six times larger than that developed when an athlete wears a three-quarter-top shoe alone and more than three times larger than that developed passively when the athlete has tape or an orthosis worn inside a three-quarter-top shoe. We conclude that fully activated and strong ankle evertor muscles are the best protection for a near-maximally inverted ankle at footstrike.

Louis Appia (1818-98): military surgeon and member of the International Committee of the Red Cross.

From Appia's writings we compose a view on his contribution to international medical relief in warfare, to the establishment of the Red Cross and the Geneva Convention, and to surgical procedures on the battlefield. Much information comes from his work on the Battle of San Martino e Solferino in June 1859 on the subject of which he wrote seven letters. We report also on his role during the Garibaldinian Campaign in 1866 and his work in Europe as a member of the International Committee of the Red Cross (ICRC).

[The pacifism of Henry Dunant]. / Il pacifismo di Henry Dunant.

From various writings of the founder of the International Red Cross and above all from his late work L'avenir sanglant it is deduced as the Dunant anticipating and prophetically interpreting the curse of the war is an internationalist (for some aspects a romantic anarchist) and a convinced pacifist. We show therefore how much has been false and backbiters the defamations that followed to the attribution of the first Nobel prize for the peace.

Rewriting of the biography of Henry Dunant, the founder of the International Red Cross.

This paper presents quite a different version of the origins of the Red Cross from that officially recognised. On the basis of historical documents and statements of authors who are critical and attentive to the detail of the circumstances and events which gave rise to the Red Cross, it is possible to discern a surprising historical truth.

Henry Dunant and Norman Bethune: a Canadian surgeon who worked with H. Dunant at the Battle of Solferino.

Following a description of both scenarios involved in the Battle of Solferino (1859), and the consequent horrors which spurred Henry Dunant to set up the International Red Cross organisation, for which he received the first Nobel Peace Prize in 1901, the present paper discusses the meeting between Henry Dunant and the Canadian surgeon Norman Bethune (1822-1892). During the days immediately after the battle, they worked together, and Bethune voluntarily operated on the injured soldiers, probably at the hospital of Brescia. In the final part, we describe the life of Norman Bethune, grandfather of the famous Henry Norman Bethune, hero of Maoist China. Norman Bethune was not only a famous surgeon in Toronto, but also Dean of the Medical School at Trinity College in 1856, a colleague of Dr George Ansel Sterling Ryerson, (recognised as founder of the Canadian Red Cross), and other members of the First Central Council of the same organisation. We suggest that Dr Norman Bethune communicated his Italian and European experience with Henry Dunant the founder of the International Red Cross, to his colleagues.

Joseph Daquin, Piedmontese Savoyard physician, a "not well-known chiarugi".

We present a critical review of La philosophie de la folie, second edition, published in 1804. Joseph Daquin's thoughts and clinical activity in the psychiatric field are described. Daquin's ideas about various forms of madness and the different therapeutic, moral, physical treatments, his anatomical studies, successes and failures are presented. Several clinical cases are described. The author's view of the moon's influence on madness is described. Finally it is shown how very important was the human person and the moral treatment of madness for Daquin, in contrast with the current opinion at the end of 1700.

[On Esquirol's historical and statistical study of the royal establishment at Charenton]. / Sur le "Mémoire historique et statistique de la Maison Royale de Charenton" de M. Esquirol.

The authors present a critical interpretation of an historical and statistical work on the Maison Royal de Charenton by M. Esquirol, three years prior to the publication of his fundamental work: "Des maladies mentales". The three historical periods of life at the Maison Royal de Charenton are described, together with the work carried out under the leadership of Esquirol during the third period. Finally, particular attention is devoted to Esquirol's statistical studies, which are re-examined in the light of present-day statistical methodologies.

Immunization of naive BALB/c mice with human beta2-glycoprotein I breaks tolerance to the murine molecule.

OBJECTIVE: Immunization of naive mice with beta2-glycoprotein I (beta2GPI) leads to the generation of pathogenic anticardiolipin antibodies associated with clinical manifestations of the antiphospholipid syndrome (APS). The aim of this study was to determine whether immunization of naive mice with human beta2GPI, which shares homology with mouse beta2GPI molecules, breaks tolerance to murine beta2GPI and leads to the generation of anti-mouse beta2GPI. METHODS: Twenty-four female BALB/c mice were immunized in the footpads with 10 microg of human beta2GPI. Twelve age- and sex-matched BALB/c mice were immunized in the same manner with Freund's complete adjuvant and served as controls. The reactivity of whole sera, polyclonal IgG, and affinity-purified anti-beta2GPI IgG antibodies against human, bovine, and mouse beta2GPI was evaluated by enzyme-linked immunosorbent assay. RESULTS: High titers of anti-human beta2GPI IgG antibodies were detected 1 month after immunization. Progressively increasing titers against murine and bovine beta2GPI were recorded 1-4 months after injection. CONCLUSION: Immunization of mice with human beta2GPI resulted in the generation of antibodies reacting with human, bovine, and murine beta2GPI. The loss of tolerance to mouse beta2GPI is attributable to the high interspecies homology of beta2GPI. These results may point to molecular mimicry as a possible cause of APS.