Mice and experimental design
Experimental arthritis was induced in 7-8 week old DBA/1J male mice (ENVIGO, Blackthorn,UK). The mice were maintained in a conventional animal housing facility at Sheba Medical Center and kept in individually ventilated cages. All experiments were approved and executed according to the protocols of the ethics committee of the Israeli Ministry of Health (no.1221/19) and fulfill “The ARRIVE guidelines 2.0” for animal research. The Collagen induced arthritis (CIA) model was performed as previously described by us [32-34]: Bovine type II collagen (Chondrex, Redmond, WA, USA) was emulsified 1:1 with mycobacterium tuberculosis H37RA in Freund’s incomplete adjuvant (Difco Laboratories, Detroit, MI, USA). DBA/1J males were subcutaneously injected into the base of the tail with 100 μg emulsion. A boost injection of bovine type II collagen in PBS, at the base of the tail, was given 21 days later. Intraperitoneal injections of IVIG (OMRIX ltd, Rehovot, Israel), 3mg/0.1 ml/mouse, started at score of 2-3 after the boost injection and repeated on a weekly base. PBS as vehicle (volume) and non-treated mice were used as controls, n = 10 per each group. The mice were sacrificed after 48 days.
Arthritis scoring The clinical scores and the hind paw widths of the mice were monitored daily over the course of each experiment. The development of arthritis was assessed daily, and the severity of arthritis was scored for each paw on a 3-point scale, in which 0 = normal appearance, 1 = localized edema/ erythema over one surface of the paw, 2 = edema/ erythema involving more than one surface of the paw, 3 = marked edema/erythema involving the whole paw. The scores of all four paws were added for a composite score, with a maximum score of 12 per mouse. Ankle thickness of the hind paws was measured in millimeters (mm) at the widest point (the malleoli) with the legs fully extended with digital calipers (Manostat, Herisau, Switzerland).

Histopathological assessment

The paws of the mice were obtained from the sacrificed mice and fixed in 4% formalin (Sigma-Aldrich St Louis, MO, USA), decalcified, cut, and stained with H&E. Samples were examined by light microscopy (×200 magnification). All histological evaluations performed by pathologists were double blinded.